oedema of feet and hands (myxoedema) Depression or cognitive slowing. Frank dementia is very rare \200 Hypore \202 exia with delayed relaxation phase; ataxia or non-speci \201 c gait disturbance Anemia. Often normocytic; less commonly macrocytic or microcytic (reduced Fe absorption) Hyponatraemia, hypercholesterolaemia, hypertriglyceridaemia \200 Symptoms of hypothyroidi sm are very common in the eu thyroid older population. Often, only treatment reveals which symptoms were due to hypothyroidism Investigation \200 Have a low threshold for thyroid function testing, in view of high dis ease incidence, poor sensitivity of clinical assessment alone, and the ease and effectivene ss of treatment Opportunistic screening of older people in primary care (eg at yearly health assessment) an d secondary care (eg on presentation to acute medical take) is probably justi \201 ed. But beware of abnormal TFTs due to sick euthyroid syndrome (see b \200\230The ageing endocrin e system \200\231, p.420) Overt primary (thyroid gland failure) hypothyroidism is con \201 rmed when TSH is high and free T4 is low. TSH elevations may be less marked in older people Subclinical or \200\230compensated \200\231 hypothyroidism is suggested when TSH is high, but free T4 is normal (although often towards the lower end of the normal range). T3 produc tion from T4 is stimulated by TSH, so may be well maintained. The patient is often asymptom atic, but may have higher risks of atherosclerosis and MI. Careful screening often reveals symptoms consistent with hypothyroidism HYPOTHYROIDISM: DIAGNOSIS 437 Thyroid masses are sometimes found on examination. USS, isotope scanning FNA will help c haracterize them. Malignant nodules are usually non-secreting ( \200\230cold \200\231), so new single nodules in a euthyroid patient merit further evaluation Anti-thyroid antibodies have reasonable sensitivity and speci \201 city in con \201 rming autoimmune hypothyroidism, and may help management in subclinical disease 2If patients have persistent lethargy despite successful treatment consider alternative dia gnoses, including other autoimmune disease, eg coeliac disease, Addison \200\231s disease, or pernicious anemia. 438 CHAPTER 15 Endocrinology Hypothyroidism: treatment \200 Overt (or \200\230clinical \200\231) hypothyroidism shoul d always be treated. The patient might believe themselves to be asymptomatic, but could fee l much improved with treatment Subclinical hypothyroidism should be treated if there are symptoms Consider treatment if: \200 TSH is particularly high, or free T3/T4 only just within norm al limits \200 Thyroid autoantibodies are positive (rate of transformation to overt hypothyroidism is much higher: 25 % compared with 5 % per annum) or there is another autoimmune condition In other cases, monitor clinically and biochemically every 6 \200\22312 months, but have a low threshold for starting what is a very safe treatment. Starting treatment \200 Begin levothyroxine (T4) at low dose \200\224 usually 25microgra ms daily. More rapid initiation risks precipitating angina, insomnia, anxiety, diarrhea, an d tremor Dosing is optimized biochemically \200\224 symptoms and signs alone are very misleading Repeat TFTs monthly or 6-weekly, increasing the dose of T4 in 25micrograms increments TSH levels guide dosage; T3 and T4 levels are not needed \200 Aim for a TSH in the mid-ra nge of normal, say 1 \200\2233 mU/L Overtreatment (TSH too low) risks AF and osteoporosis \200 Undertreatment risks physical and cognitive slowing, weakness and depression Older people usually require slightly less T4 \200\224 usually 50 \200\223125micrograms daily is suf \201 cient Heavier people require proportionately more T4 than lighter people \200 T4 half-life is a round 1 week. Therefore, if \201 ne-tuning of dosing is needed, simply alternate higher and lower doses, eg 100/125micrograms on alternate days Long-term management \200 Tell the patient that treatment is for life \200 Check thyroi d function every year and if clinically indicated \200 In the very long term, thyroxine r equirements may rise, fall, or remain unchanged Administration \200 Foods reduce absorption \200\224 take on an empty stomach, usually \201 rst thing in the morning If a dose is missed, take it as soon as remembered, and the next dose as normal If compliance is a problem, twice weekly or weekly administration (of proportionately higher doses) gives acceptable control HYPOTHYROIDISM: TREATMENT 439 Thyroxine \200\224 interactions with other drugs \200 Antiepileptics (phenytoin, primido ne, and carbamazepine), barbiturates and rifampicin increase thyroid hormone metabolism, so a higher T4 dose may be needed Colestyramine, iron, calcium, and antacids (eg aluminum hydroxide) reduce T4 absorption. Give T4 at least 2hr beforehand Amiodarone has complex effects. Monitor TFTs regularly. (See b \200\230HOW TO Manage amiodarone-induced thyroid dysfunction \200\231, p.139) B -blockers may reduce conversion of T4 to T3 Disease \200\223drug interactions As thyroid disease is controlled, dose changes of the fol lowing may be needed: diabetic drugs (insulin and oral hypoglycaemics), digoxin, warfarin, theophylline, corticosteroids . 440 CHAPTER 15 Endocrinology Hyperthyroidism: diagnosis Subclinical hyperthyroidism is more common in older people (prev alence 3 % ), but severe disease is less common (incidence 0.1 % per year in older women, 0 .01 % per year in older men). Causes \200 Toxic nodular goiter . The most common cause in older people. There is often slow (years) progression from smooth goiter (euthyroid) to multinodular goiter (euthyroid). Then nodule(s) begin autonomous function, with subclinical and then clinical hyperthyroidi sm. It does not remit, but may be relatively mild and indolent Graves \200\231 disease . The thyroid is stimulated by autoantibodies. Exophthalmos and diffuse goiter are less common than in younger people; 40 % have no palpab le goiter. Many remit within a year, perhaps more so than in younger patients Exogenous levothyroxine , ie overtreatment of hypothyroidism. This usually occurs insidiously when age-related slowing in T4 metabolism is not paralleled by r eductions in the dose of T4. Less common causes include: Amiodarone (see b \200\230Amiodarone \200\231, p.138), and other sources of excess iodine Subacute thyroiditis and Hashimoto \200\231s thyroiditis . There is transient thyroid hormone excess due to gland destruction. Suspect if acute hyperthyroidism occurs wi th sore throat or tender neck. There may be an associated viral syndrome or upper respirato ry tract infection Single autonomous nodule (Plummer \200\231s disease) \200 Malignant T4-secreting thyroid tumors and pituitary/non-pituitary TSH- secreting tumors 2Distinguishing between the two very common causes (toxic nodular goiter and Graves \200 \231 disease) is relatively unimportant, as treatment is similar. However, always consider the possibility of drugs (thyroxine or amiodarone) or acute thyroiditis, where treatment is clearly different. Presentation In older people with overt hyperthyroidism: \200 Presentation may be more su btle, with fewer symptoms and signs \200 Diagnosis is often delayed. Features are attribu ted to comorbidity or suppressed by B -blockers \200\230Negative \200\231 symptoms may dominate ( \200\230apathetic hyperthyroidism \200 \231), eg anorexia, weight loss, fatigue, weakness, and depression. Non-speci \201 c sympt oms are more common eg nausea, weakness, functional decline \200 More classical symptoms of sympathetic overactivation may be absent eg tremor, restlessness, sweating, tachycardia and hypertension \200 Cardiovascular compl ications are more common, eg angina, heart failure, AF (although ventricular response may be slow) Constipation is more common than diarrhea \200 Increased bone turnover leads to hypercalc aemia and osteoporosis HYPERTHYROIDISM: INVESTIGATION 441 Hyperthyroidism: investigation Thyroid function tests \200 Have a low threshold for testi ng in older people, especially if there is a personal or family history of thyroid disease Screening is recommended by some \200\224 at least every 5 years in women > 60 Low TSH is sensitive but not speci \201 c to hyperthyroidism Drugs or non-thyroidal illness can suppress TSH below normal, but it usually remains detectable (0.1 \200\2230.5mU/L) Very low TSH levels (<0.1mU/L), indicating total suppression of TSH secretion, are more speci \201 c to hyperthyroidism Overt hyperthyroidism In most cases, TSH is undetectable and both T4 and T3 are high \200 Elevated T3 without T 4 ( \200\230T3 toxicosis \200\231) suggests toxic nodules or relapsing Graves \200\231, and is treated as hyperthyroidism Elevated T4 but normal T3 (due to reduced peripheral conversion) suggests intercurrent illness In severe hyperthyroidism, T4 may be normal (reduced binding globulin). Free T4 remains high Acute systemic illness in euthyroid people may cause transient (days) elevation of T4. TSH will be normal or moderately low Subclinical hyperthyroidism This is common: up to 5 % point prevalence of decreased TSH in healthy older people. TSH levels are low, with normal (often high normal) free T3 and T4 In most cases, TSH levels revert to normal within a year \200 Progression to overt hypert hyroidism occurs in <10 % per year \200 Symptoms are few, but there is an increased risk of osteoporosis, AF, LVH, and possibly dementia Consider the possibility that non-thyroidal illness (rather than thyroid hormone excess) ma y be suppressing TSH production Anti-thyroid antibodies \200 Their presence supports a diagnosis of Graves \200\231 disea se, especially if a smooth goiter is also palpable, but they are not wholly speci \201 c Antibody tests are usually negative in toxic nodular goiter \200 Graves \200\231 and toxi c nodular goiter are both common and can coexist. In that case a nodular goiter may be palp able, with positive antibodies \200 If Graves \200\231 disease is likely, screen for pern icious anemia and coeliac disease (using relevant autoantibody tests and vitamin B12 levels ) Thyroid radioisotope scanning This can help con \201 rm the cause of hyperthyroidism and t o determine glandular size prior to radioiodine treatment. \200 In thyroiditis, uptake is low or very low. In \202 ammatory markers are up \200 In Graves \200\231, there is a di ffuse pattern of increased uptake \200 In toxic nodular goiter, there are multiple \200 \230hot \200\231 nodules with surrounding \200\230cold \200\231 tissue A single autonomous \200\230hot \200\231 nodule is surrounded by \200\230cold \200\231 ti ssue 442 CHAPTER 15 Endocrinology Hyperthyroidism: drug treatment Overt hyperthyroidism should always be treated, even if mil d. Several options are available for immediate and long-term treatment. Select on an individua l basis, depending on the likely diagnosis, severity of illness and patient characteristics , and preferences. Drug treatment: thioamides (carbimazole or propylthiouracil) \200 Suitable for initial ma nagement of Grave \200\231s disease or toxic nodular goiter In Graves \200\231 disease this is an option for long-term therapy, as there is a greater p robability of long-term remission than in younger people. Duration of treatment is usually 18 months, after which treatment is stopped and regular monitoring continues. Relapse risk is 50 % and is more likely if disease is severe, there is a large goiter, or antibody leve ls are high. If relapse occurs, begin thioamides again, and refer for de \201 nitive treat ment (usually radioiodine) In toxic nodular goiter , long-term remission is less commonly achieved using thioamides. They are therefore used either: \200 Short-term, to achieve euthyroidis m prior to de \201 nitive treatment (usually radioiodine) Long-term, in the frail patient in whom life expectancy is short \200 Initial daily dose: carbimazole 20 \200\22340mg, propylthiouracil 200 \200\223400mg (once daily or divided dose) Full thyroid suppression takes several weeks. Continue the initial dose for 4 \200\2238 wee ks, until euthyroid. Measure free T4 every 2 weeks to assess when euthyroid state is achiev ed as TSH may be suppressed for months despite adequate treatment Once control is achieved, there are two options, with similar outcomes: \200 Titration regimen . Thioamide dose is reduced gradually, guided by TFTs, t o a maintenance dose of carbimazole 5 \200\22315mg or propylthiouracil 50 \200\223150mg dai ly Block and replace regimen . Thioamide dose is maintained high, entirely switching off thyro id synthetic function. Introduce levothyroxine once free T4 is suppressed Side effects include: Skin rash or pruritus. Continue treatment. Try antihistamines. Try switching thioamides Fever, arthralgia, headache, and gastrointestinal symptoms are usually mild Agranulocytosis. This is uncommon, but more frequent in older people. Usually occurs early in treatment. Check FBC regularly (monthly until stable). It is vital to advise patient and /or relative that the drug must be stopped and urgent advice sought if fever, sore throat, mouth ulcers, or other symptoms of infection develop HYPERTHYROIDISM: DRUG TREATMENT 443 Drug treatment: B -blockers \200 Used for rapid symptomatic treatment (tremor, anxiety, a ngina) and to reduce the risk of dysrhythmia. There is no effect on the hypermetabolic stat e itself May be especially useful in those with known structural or ischaemic heart disease or who a re tachycardic, but should be introduced cautiously, with regular monitoring. Digoxin is in effective in controlling AF in hyperthyroidism Check carefully for contraindications (eg asthma) \200 All B -blockers are effective. Ate nolol is a good choice, as it may be given od. Metoprolol and propranolol must be given tds or qds (increased hepatic metabol ism in hyperthyroidism) They have a role: In Graves \200\231 or toxic nodular goiter as an adjunct to thioamides \200 Where hyperth yroidism is only mild, B -blockers may be the only drugs needed prior to de \201 nitive tr eatment with radioiodine \200 In thyroiditis. The hyperthyroid state is transient, and B -blockers alone may be suf \201 cient treatment until the disease moves onto euthyroidism or hypothyroidism Subclinical hyperthyroidism \200 If due to excess T4 in a patient with treated hypothyroi dism, reduce dose by 25micrograms and recheck TFTs in 6 weeks In other cases, in order to protect bone, heart, and brain, consider treatment as for overt hyperthyroidism. This is especially indicated if: \200 There is os teopenia or heart disease, or signi \201 cant risk factors \200 Suppressed TSH is persis tent, or severe, or T3/4 levels are at the higher limits of normality If treatment is not begun, reassess every 3 \200\2236 months Atrial \201 brillation and hyperthyroidism \200 Occurs in 10 \200\22315 % . Most revert to sinus rhythm within weeks of becoming euthyroid, unless AF has been present for many months \200 Digoxin is usually in effective in controlling ventricular rate. B -blockade is more effective Consider cardioversion if AF persists for 4 months in new-onset AF \200 Anticoagulate wit h warfarin to target INR 2 \200\2233. While hyperthyroid, patients are relatively hypersensitive to warfarin See b \200\230Atrial \201 brillation \200\231, p.276. Amiodarone and thyroid disease Incidence of amiodarone-induced thyroid disease is high in o lder people because of this cumulative exposure and the drug \200\231s very long half-life. \200 Clinical assessment alone is insensitive. Check TFTs before amiodarone treatment, and then every 3 \200\2236 months. If amiodarone is stopped, continue TFT monito ring for several years For the clinical features and management of amiodarone-induced hypo- and hyperthyroidism, see b \200\230HOW TO Manage amiodarone- induced thyroid dysfunc tion \200\231, p.139 444 CHAPTER 15 Endocrinology Hyperthyroidism: non-drug treatment Radioiodine (I 131 ) \200 Radioiodine is effective, w ell tolerated, safe, and simply administered. The sole contraindications are: \200 When safe disposal of radioactive body \202 uids a fter treatment cannot be guaranteed (eg home drainage is not into the main sewer) This can usually be overcome In early treatment of hyperthyroidism, when administration of the iodine load can precipitate thyrotoxic crisis Radioiodine is especially useful if there are drug intolerances, polypharmacy, or comorbidities Give once initial symptomatic control has been achieved with drugs \200 Thioamides must b e stopped several days before administration of radioiodine (to permit uptake) and are usually restarted several days after (to prevent thy roid storm). Permanently discontinue thioamides after 3 \200\2234 months if TFTs are satisf actory Estimating the dose of I 131 required to render a patient euthyroid is dif \201 cult \200 On average, larger doses are needed for patients with toxic nodular goiter ( cf. Graves \200\231), larger goiters, in severe disease and in men \200 Most cen ters give a single larger dose (400 \200\223600MBq) that controls hyperthyroidism in most c ases, but leads to early hypothyroidism in up to 50 % . A second dose is needed for a minor ity who remain hyperthyroid Post-treatment, TFTs should be checked every 4 \200\2236 weeks for the \201 rst year, and then lifelong at reduced frequency but at least every year for life Secondary hypothyroidism may occur early (weeks, often transient)) or late (years). Eventua lly up to 90 % become hypothyroid. There may be an early (weeks) rise in TSH that is transi ent and does not need treatment if there are no symptoms If the patient remains hyperthyroid at 6 months, then repeat I 131 dosing is usually needed Surgery This is rarely performed in older people, considered only if both drug and radioiod ine treatment are problematic, or if a large goiter is especially troublesome. The patient must be euthyroid before surgery; B -blockade alone is not suf \201 cient. Lifelong postop erative thyroid function monitoring is essential. HYPERTHYROIDISM: NON-DRUG TREATMENT 445 Life-threatening thyroid emergencies Thyroid storm A rare but life-threatening manifestation of hyperthyroidism \200 Most comm only seen in patients with undiagnosed hyperthyroidism, often precipitated by non-thyroidal illness (including surgery, sepsis, or trauma) or administration of iodine-containing drug s Very rarely seen after radioiodine treatment \200 Features include delirium, restlessness , coma, fever, vomiting, heart failure, tachycardia, and myocardial ischaemia The diagnosis is clinical \200\224 TFTs are often no worse than in typical hyperthyroidism Support failing organs, treat the underlying cause(s) and seek urgent specialist advice Antithyroid drugs and iodide may be given intravenously to reduce thyroid hormone synthesis B -blockers and corticosteroids reduce the peripheral activity of thyroid hormones Myxoedema coma A rare but life-threatening manifestation of hypothyroidism \200 More comm on in older people, presenting as circulatory and respiratory failure and progressive drowsiness leading to coma, often with \201 ts There is usually an acute precipitant (eg infection) in a patient with chronic hypothyroidism Think of this also in patients who have stopped taking or absorbing levothyroxine 446 CHAPTER 15 Endocrinology Primary adrenal insuf \201 ciency Also known as Addison \200\231s disease. Presentation Usually insidious and often non-speci \201 c onset: \200 Symptoms include f atigue (helped by rest), weight loss, anorexia, abdominal pain, nausea, constipation, hypotension (orthostatic and supine), depression, del irium, and decreased functional status Skin and mucous membrane hyperpigmentation is common, but is a late sign and may be absent. Pigmentation affects sun-exposed and unexposed areas, especially scars and pressure points Electrolyte disturbance (hyponatraemia and hyperkalaemia) and a mild acidosis (bicarbonate 15 \200\22320mmol) are usually present. Hypoglycaemia and mild anemia may be present 2In some people with impaired adrenocortical function, there may be no symptoms when well, but acute stress (trauma, illness, psychological) leads to adrenal crisis with shock. If th e possibility of adrenal insuf \201 ciency crosses your mind, then test for it, with a sho rt ACTH stimulation test. Causes \200 Mostly autoimmune. Often evidence of other autoimmune disease \200 TB is re latively more common in older people \200 Uncommonly due to: metastases, lymphoma, hemorr hage or infarction. Very rarely due to: drugs, eg ketoconazole Diagnosis Serum cortisol Cortisol is secreted episodically, so do not make or exclude a dia gnosis on the basis of a single measurement \200 A very low cortisol level (<100nmol) mak es adrenal insuf \201 ciency likely, especially if the patient is stressed/unwell at the time A moderately high ( > 300nmol) cortisol level makes adrenal insuf \201 ciency unlikely In Addison \200\231s, a random cortisol may be low or normal, ie normal level does not exclude Addison \200\231s Early morning (6 \200\2238am) cortisol levels should be higher \200\224 a low level is more likely to be signi \201 cant Short ACTH stimulation test ( \200\230Synacthen test \200\231). The only test that has good sensitivity and speci \201 city. See b \200\230HOW TO Perform a short ACTH sti mulation test (short Synacthen test) \200\231, p.411 Adrenal autoantibodies are positive in many autoimmune cases \200 AXR and CXR may show si gns of TB (eg calci \201 cation) \200 Adrenal CT or MRI reveals a small gland in autoimm une disease, large if infection or tumor If adrenal insuf \201 ciency is diagnosed, exclude secondary adrenal insuf \201 - ciency (pituitary failure). \200 Check gonadotrophins (follicle-stimulating hormone, luteinizing hormone, and TSH ACTH is elevated in primary adrenal insuf \201 ciency, low in secondary PRIMARY ADRENAL INSUFFICIENCY 447 Treatment If the patient is unwell, do not delay treatment pending the results of tests: \202 uid resuscitate with iv normal saline, normalize electrolytes, and give high-dose iv o r im hydrocortisone (100mg tds). Improvement should occur quickly. Long-term treatment includes oral glucocorticoids (usually hydro- cortisone 20mg am, 10mg p m) and mineralocorticoids (usually \202 udrocor- tisone 0.1mg). On treatment, older people are much more likely to develop hyperten- sion that may require mineralocorticoid dose reduction and non-diuretic antihypertensive drugs. Older people have a worse prognosis, due to more sinister causation (TB, malignancy) and possibly later presentation. Adrenal \200\230incidentalomas \200\231 \200 An \200\230incidentaloma \200\231 is a tum or detected by scanning (ultrasound, CT, or MRI) that is unrelated to the indication for the scan Adrenal incidentalomas are relatively common (0.5 \200\2231 % of scans) They are more common in older people and the hypertensive. Key questions are \200\230Is it malignant? \200\231 and \200\230Is it functional? \200\231 Adrenal insuf \201 ciency does not occur unless both glands are almost totally destroyed Signs of a functional nodule include hypertension and hypokalaemia Adrenal adenomas are ver y common and usually small (<2cm), benign and non-functional. Fine-needle biopsy helps excl ude malignancy if scan appearances are worrying, but usually only observation (periodic sca n- ning) is needed. The larger the tumor, the higher the chance of malig- nancy. Large tumo rs should generally be excised, as biopsy may not identify foci of malignancy. Metastases are common (primary: breast, bronchus, bowel). Scan appearances are usually diagnostic. Cysts and lipomas make up most of the remainder. Benign adrenal cysts are common in older p eople and may be due to cystic degeneration or local infarction. Tuberculosis may seed haematogenously, causing adrenal masses, often calci \201 ed. Non-functional adrenal carcinoma usually presents late, with retroperitoneal spread and distant metastases. 448 CHAPTER 15 Endocrinology Hormone replacement therapy and the menopause The menopause (cessation of menstruation due to ovarian failure) occurs typically between ages 45 and 55. The diagnosis can usually be m ade clinically. If the presentation is atypical, consider alternative diagnoses, eg hyperth yroidism. Following menopause, the risk of osteoporosis and vascular disease increases subs tantially. Symptoms can occur for several years before and after menopause and can be disab ling. They include: \200 Hot \202 ushes \200 Genitourinary atrophy \200 Insomnia, d epressed mood, and cognitive symptoms HRT with estrogen (plus progestogen in those with an intact uterus): \200 Is an effective treatment for peri-menopausal symptoms \200 Does n ot improve well-being in those with no symptoms \200 Does not improve cognitive function or prevent dementia \200 Increases the risk of stroke, coronary events, pulmonary embolis m, and breast, ovarian, and endometrial cancer. Increased risk (cumulative serious events) is 1 in 1000 if treated for 1 year, 1 in 100 if treated for 5 years Reduces colon and rectal cancer and hip fracture by small amounts, but is no longer recommended for osteoporosis treatment In those with menopausal symptoms: Consider non-systemic treatments , eg topical oestrogens for atrophic vaginitis (vaginal cr eam or tablets, given daily for 2 weeks, then once or twice weekly for 6 \200\2238 weeks; s ometimes needed long term). There is some systemic absorption; the risk of endometrial canc er is unknown. In those with reduced manual dexterity, consider a slow-release vaginal ring (replaced after 90 days) Other drugs that can help, but are less effective than systemic oestrogens include: \200 Progestogens, eg medroxyprogesterone, megestrol \200 Herbal remedies, som e of which may have estrogen-like activity \200 Clonidine (an A -adrenoceptor stimulant; usual dose 50 \200\22375micrograms bd) may reduce hot \202 ushes. Side effects are often problematic. Watch BP If symptoms continue, consider HRT , explaining the risks and bene \201 ts. \200 Start t reatment at low dose, increasing gradually until symptoms are controlled Explain that HRT is a short-term, and not inde \201 nite, treatment \200 Every few month s, taper the dose of HRT, assessing whether ongoing treatment is needed. Hot \202 ushes u sually cease after a few months to a few (<5) years HORMONE REPLACEMENT THERAPY AND THE MENOPAUSE 449 Increasing numbers of women have taken HRT for very prolonged periods and are being seen mo re frequently in geriatric practice. In each case, the risks and bene \201 ts of continuin g HRT must be assessed. In most cases, the advice will be to stop HRT: \200 Risk is proba bly cumulative (dose and duration) \200 Risk is probably multiplicative (non-HRT risk \227 HRT-related risk). As background risk of cancer and vascular disease rises exponential ly in older people, so the net added risk of HRT is higher in older people In most cases, HRT may be withdrawn without recurrence of menopause symptoms In most cases, HRT will have been started (and the patient last advised) when the risks were not appreciated 2HRT is an effective treatment for symptoms, but has potentially serious side effects. Further reading Crawford F , Langhorne P . ( 2005 ). Time to review all the evidence for ho rmone replacement therapy . BMJ 330 : 345 . This page intentionally left blank 451 Chapter 16 Hematology The ageing haematopoietic system 452 Investigating anemia in older people 453 Iron de \201 ciency anemia: diagnosis 454 HOW TO Investigate iron de \201 ciency anemia 455 Iron de \201 ciency anemia: treatment 456 Macrocytic anemia 457 Anemia of chronic disease 458 Paraproteinaemias 459 Multiple myeloma 460 Myelodysplasia and myelodysplastic syndrome 462 HOW TO Transfuse an older person 463 Chronic lymphocytic leukemia 464 452 CHAPTER 16 Hematology The ageing haematopoietic system There are very few changes as the bone marrow ages. Be ver y reluctant to ascribe changes seen on testing to age alone \200\224 pathology is much mor e likely. Hemoglobin \200 Epidemiological studies show that population hemoglobin (Hb) concentration gradually declines from age 60 There is debate as to whether the reference range should be adjusted since lower Hb levels are associated with increased morbidity and mortality compared with older patients who main tain normal levels \200 Thus anemia is common in old age (between 10 \200\22320 % will ha ve Hb less than 12g/dL in females or 13g/dL in males), but this is due to disease(s) not ag eing per se The decision about whether to investigate anemia should be made not on the absolute value but the clinical scenario. Consider symptoms, past medical histor y, severity of anemia and rate of fall of Hb, the mean cell volume (MCV) and \201 nally p atient \200\231s wish/tolerance of investigation A \201 t elderly man with no signi \201 cant past history merits investigation with an H b of 11.5 g/dL (especially if his Hb g/dL was 13 last year or if the MCV is abnormal) while a patient with known rheumatoid arthritis, renal failure and heart failure who has a normo cytic anemia 10.5 g/dL for years usually does not Erythrocyte sedimentation rate (ESR) \200 The height of the red cells in a standard bottl e of blood, after being allowed to sediment for 60min This is a simple, old fashioned and non-speci \201 c test however it is inexpensive and remains useful for screening and monitoring disease in older people. CRP is often used in conjunction Red cells fall gradually because they are more dense, but the rate of fall increases where the cells clump together ESR rises with age and is slightly higher in women so values up to 30mm/hr for men and 35mm/hr for women can be normal at age 70 Anemia can cause a mild elevation in ESR \200 A high ESR occurs in disorders associated w ith elevated plasma proteins ( \201 brinogen and globulins). Numerous acute and chronic disorders can cause mo dest elevation Very high levels ( > 90) are commonly found with paraproteinaemias, giant cell arteritis and chronic infections such as tuberculosis INVESTIGATING anemia IN OLDER PEOPLE 453 Investigating anemia in older people A low hemoglobin is a frequently encountered abnormali ty in geriatric practice. It is worth remembering the following: \200 Other parameters, u sually documented in the full blood count report (eg MCV) will greatly assist in characteri zing the anemia, and should be scrutinized Looking up old FBC results will often reveal a pattern eg a frail older person may run a ch ronically low Hb because of chronic disease or marrow failure. If there is a recent change, this should prompt more urgent investigation Unwell older patients may have low Hb as a result of \202 uid overload or marrow suppress ion. Repeat FBC as they recover, and see if it persists \200 Multiple etiology is common, so check a full range of blood tests in all anemic older patients It is very important to check that the laboratory have received the correct blood specimens for these tests before arranging blind replacement therapy or a transfusion \200\224 subs equent samples will be invalid for haematinics Most anemic patients will require: \200 Blood \201 lm \200 Ferritin, serum iron and t otal iron binding capacity (or transferrin) \200 B12, folate \200 Renal, liver and thyr oid function testing \200 Blood and urine electrophoresis and look for Bence Jones protei ns in urine if the ESR is raised If the anemia has been characterized (eg iron de \201 cient, macrocytic etc.), then decisi ons can be made about the nature and extent of further testing. See b \200\230Iron deficie ncy anemia: diagnosis \200\231, p.454 for details. If the picture is mixed, then there may be multiple contributing factors (eg chronic kidney disease, minor gastritis, early myelodysplasia) \200\224 list these and address each in t urn. 454 CHAPTER 16 Hematology Iron de \201 ciency anemia: diagnosis This is the most common cause of microcytosis (but b eware the occa- sional patient with lifelong microcytosis who has an inherited thalassaemia or sideroblastic anemia). Causes \200 Most common is occult blood loss in the gut especially in patients taking NSAIDs (even 75mg aspirin) Malabsorption (eg coeliac disease, gastrectomy, achlorhydria due to atrophic gastritis or use of PPIs) Malnutrition as a sole cause is very unusual 2Multifactorial etiology is common \200\224 e g mild chronic blood loss, border- line dietary intake and mild malabsorption syndromes Diagnosis History is vital (ask about weight loss and gut, kidney, urogenital, or ENT blood loss). Pallor (conjunctivae, nail beds) may be found. The emphasis of examination should b e to \201 nd rectal or abdominal masses, hepatome- galy, and lymphadenopathy. Investigations \200 Microcytosis usual but not in combined de \201 ciency or acute blood loss \200 Low serum ferritin levels (<12micrograms/L) are diagnostic. Moderately low levels (12 \200\22345micrograms/L) may also point to the diagnosis as ferrit in levels rise with age. Ferritin is an acute phase reactant so normal/high levels don \200 \231t rule out de \201 ciency Serum iron levels will be low with high iron binding capacity, ie the ratio of iron/iron bi nding will be low (<15 % ). This is a useful way of distinguishing the anemia of chronic di sorder where both iron and iron binding are low (and the ratio will be normal) (see also Ta ble 16.1 ) Low iron stores on a bone marrow trephine are diagnostic but this investigation is painful and rarely required Fecal occult blood is of limited value in cases of established iron de \201 ciency \200 \224 it is usually positive and you may feel that further gastrointestinal tests are needed anyhow Table 16.1 Characteristic \201 ndings in iron de \201 ciency and chronic disease Test Iron de \201 ciency Chronic disease MCV Microcytic Normocytic Iron Low Often low Transferrin or total iron binding capacity (TIBC) Normal or high Low Iron: TIBC ratio Low (<15 % ) Normal Ferritin Low is diagnostic Normal or high IRON DEFICIENCY anemia: DIAGNOSIS 455 Haematuria suf \201 cient to cause anemia is rare, and usually severe. Urinalysis may be indicated in patients with poor vision or cognition to look for renal tra ct blood loss Iron de \201 ciency without anemia should still be investigated but the lower the Hb the higher the likelihood of \201 nding attributable pathology HOW TO Investigate iron de \201 ciency anemia The main dilemma is deciding how far t o take investigations. A \201 t patient , who would be a candidate for surgery, should have a minimum of OGD and colon imaging ( see b \200\230HOW TO Image the older colon \200\231, p.373). These should proceed regardless of the degree of anemia and whether there are symptoms. The \201 nding of oesophagitis or an upper gastrointestinal ulcer should not stop a screening t est for the colon to rule out a coexisting neoplasm. If these tests are negative, screen fo r coeliac disease (eg endomysial antibody) and haematuria. Small bowel barium studies or ca psule endoscopy are sometimes helpful. If there is intermittent overt gastrointestinal bloo d loss mesenteric angiograms can demonstrate small angiodysplastic lesions if there is acti ve hemorrhage. At the other extreme a frail, bed-bound nursing home patient with dementia will probably me rit empirical iron and PPI therapy without further investigations. In between these extremes physicians often adopt a \200\230half way house \200\231. Some examples of this compromise include: \200 Not proceeding to lower ga strointestinal tests if upper gastrointestinal pathology is found Where NSAIDs are the likely problem, stop the drug, give iron, and a PPI, and only investig ate if the anemia or evidence of bleeding continues after a suitable therapeutic trial Not performing lower gastrointestinal tests if the patient is not \201 t for, or not consenting to surgical intervention Performing a \202 exible sigmoidoscopy rather than a full colonoscopy (80 % of tumors can be excluded this way without complete bowel preparation and with less risk and discomfort) Using oral contrast-enhanced CT colography to image the colon (better tolerated) will miss small lesions but excludes large tumors \200 Assuming that v ery longstanding and stable iron de \201 ciency (several years) presents low risk for a malignant source There are no hard rules about making these decisions but it is advis- able that any risk-ta king is shared with the patient and/or relative and that you record your discussions in the notes. Remember that: \200 Investigations are often better tolerated than you would expe ct, eg OGD remains a very safe test even in very old people Sometimes it is worth doing tests even if de \201 nitive treatment is not available, eg for a frail patient with bloody diarrhea a sigmoidoscopy may yield an alterna tive diagnosis or guide future palliative therapy A second medical opinion may help Most patients are highly persuadable \200\224 if you do want them to take an active part in decisions you will need to give an unbiased view of the ir options \200\224 \200\230You don \200\231t want one of those unpleasant dangerous endo - scopies do you? \200\231 does not present the patient with a fair choice. 456 CHAPTER 16 Hematology Iron de \201 ciency anemia: treatment Treatment is often simple. Treat the underlying caus e, and replenish iron stores. The underlying marrow is usually healthy. Hb should rise by a bout 0.5g/dL/week. Blood transfusion is expensive, usually unnecessary and can be dangerous. It should be used only for severe symptoms (eg unstable angina) or where ongoing acute bleeding is present. Enteral iron \200 Oral supplements (ferrous sulfate 200mg od to tds) are very effective but compliance is often poor due to gastrointestinal side effects (constipation, nausea, di arrhea) Sometimes a different preparation (ie ferrous gluconate or fumarate) is better tolerated Start with low dose and increase as tolerated. It is better to take a lower dose for longer than abandon treatment after a few days due to side effects. Alternat e day supplementation is often suf \201 cient If stool is not greeny-black, concordance is poor \200 Avoid slow-release preparations, a s they are often poorly absorbed \200 Remember that achlorhydria (atrophic gastritis or P PI administration) signi \201 cantly reduces iron absorption Failure to respond to enteral iron This should prompt consideration of the following: \200 Is there ongoing hemorrhage? \200 Is the patient concordant with therapy? \200 Are th ere other contributory factors (eg kidney disease) \200 Is the iron being absorbed? Parenteral iron therapy \200 Use is increasing with the development of safer preparations \200 Consider if blood loss exceeds ability of gut to absorb oral iron (eg with angiodysplasia), the patient does not tolerate oral iron, or the oral iron is not adequately absorbed (eg with atrophic gastritis) Also used in renal patients on erythropoietin (need adequate iron for response) and those with in \202 ammatory bowel disease (often intolerant of oral iron)