Secondary hypothyroidism (due to hypothalamo-pituitary failure) causes a similar pattern of TFTs, but is very much less common, and other features of pitui tary failure are present (eg hypogonadism) In the convalescent phase following illness, TSH may be elevated as low thyroid hormone lev els drive TSH production. For a time, TSH may be high and T4/T3 low, mimicking primary hypo thyroidism. TFTs repeated a few weeks later are usually normal. Ageing and glucose metabolism In older people: \200 Glucose-induced insulin release is de layed and reduced in size \200 Insulin-induced suppression of hepatic glucose production is delayed \200 Insulin-mediated peripheral (muscle and fat) glucose uptake is reduced In addition to reductions in physical activity and lean muscle mass, the factors listed here lead to higher frequency of impaired glucose tolerance (IGT) with age. IGT is associated wi th macrovascular disease but not with speci \201 c diabetic complications. A minority of p eople with IGT progress to diabetes. This page intentionally left blank 422 CHAPTER 15 Endocrinology Diabetes mellitus Diabetes is much more common with age: about 40 % of new diagnoses are in people over 65. Prevalence in people over 65 is 10 % in the UK, up to 50 % in some ethnic groups and obese patients. Comparing type 1 and type 2 diabetes \200 Both type 1 (insulin \200\223dependent; IDDM) a nd type 2 (non-insulin dependent; NIDDM) diabetes can occur in older people. The prevalence of type 2 is much higher In overweight older people, diabetes is mostly due to peripheral tissue insulin resistance (type 2). Glucose-induced insulin release is normal \200 Lean older people with diabetes often have impaired insulin release and may have islet cell antibodies more typical of type 1 diabetes. They respond poorly to oral hypoglycaemics There are increasing numbers of older people with type 1 diabetes who developed the disease in early or mid-life and have survived decades on insulin, sometimes with no or few compli cations Many people with type 2 diabetes progress to require insulin to achieve acceptable glycaemi c control. This group is insulin-requiring (hence IRDM) and are unlikely to develop ketoaci dosis if insulin is withdrawn When assessing a patient on insulin, determine whether they are insulin-dependent (type 1; must always have background insulin infused) or insulin-requiring (type 2; in which insulin may safely be withheld for a time, without risk of ketosis) Secondary diabetes More common in older people. Causes include: \200 Drugs. Often steroid s, sometimes high-dose thiazides, rarely other drugs Pancreatic disease, eg chronic pancreatitis \200 Other endocrine diseases, eg Cushing \200\231s, hyperthyroidism Presentation \200 Diabetes often presents atypically or late in older people \200 Up to 50 % of older people with diabetes are undiagnosed. This is at least partly due to physiological age-related changes, eg the renal threshold for glucos e increases (glucosuria and polyuria occur later) and the thirst mechanism is impaired (pol ydipsia occurs later) \200 The diagnosis is often made by screening blood or urine tests, or during intercurrent illness Think of diabetes in many clinical circumstances, eg coma, delirium, systemic stress (eg pneumonia), oral or vaginal thrush (candida), vulval itch (subclinical candida), cellulitis (and necrotising fasciitis), weight loss, urinary incontinence, polyur ia, malaise, vascular disease or peripheral neuropathy Steroid administration may reveal a diabetic tendency \200\224 always monitor, especially when high doses are used DIABETES MELLITUS 423 HOW TO Diagnose diabetes in older people \200 Con \201 rm the diagnosis with a ran dom blood sugar or fasting sugar. Criteria are the same as for younger patients In general, the diagnosis is con \201 rmed with a second measurement, unless the diagnosis is clear (eg severe hyperglycaemia with metabolic decompensation). A s ingle high measurement in the absence of symptoms is not diagnostic In some older diabetic people, fasting sugars may be normal. This is more common in lean ol der people, who have only postprandial hyperglycaemia. If in doubt, do an oral glucose tole rance test Elevated glycosylated hemoglobin (HBA 1c ) levels are only moderately speci \201 c and sensitive to diabetes and are not suf \201 cient either to co n \201 rm or to exclude the diagnosis. HBA 1c is helpful in monitoring established disease Screen annually in those with risk factors (eg family history, obesity), at least every 3 years in those without Diagnostic criteria At least one of the following criteria must apply: \200 Symptoms + ra ndom plasma glucose > 11.1mmol \200 Fasting plasma glucose > 7.0mmol \200 2-hr plasma g lucose > 11.1mmol during oral glucose tolerance test (75g anhydrous glucose or the equivale nt volume of a proprietary glucose drink such as Lucozade) Obtaining a fasting blood sugar \200 Give the completed request card to the patient \200 The patient should make an early morning appointment with a phlebotomist or general practice nurse There must be no caloric intake for at least 8hr before the blood test Tell the patient to go for the blood test before breakfast \200 Clear \202 uids (water; tea or coffee without milk or sugar) may be taken Other beverages or food must be avoided 424 CHAPTER 15 Endocrinology Diabetes: treatment \200 In all patients, aim to avoid symptoms of hyper- and hypoglycaem ia \200 In the more robust older patient, good glycaemic control probably reduces complication rates: \200 Aim for HBA 1c levels close to normal (6.5 \200\2237.5 % ) and fasting sugar of 5 \200\2237mmol/L The frail, and the very old ( > 80 years) have not been included in most prospective treatm ent studies. There is therefore doubt whether tight glycaemic control improves long-term ou tcome. Shorter-term bene \201 ts may include improved cognition, functional status, mood, and vitality \200 Balance the potential bene \201 ts of tight control with the risk of d rug-induced symptomatic hypoglycaemia, falls, and fractures Symptoms of hypoglycaemia may go unrecognized or be considered an ageing change by carers Reasonable targets for the frail are HBA 1c 7.5 \200\2238.5 % and fasting sugar 7 \200\22310mmol/L Vulnerable older patients are probably at higher risk of hypoglycaemia (eg causing confusion and falls) than hyperglycaemia. In some circumstances (eg where gluco se levels appear very variable) it may be safest to accept very high ceiling levels (eg up to 20mmol/L) 2In general, in frail older people, the approach is to reduce symptoms, not to normalize sugars. Diet \200 Dietary change is often the only treatment needed in obese people with type 2 diabetes Wholesale changes to diet may not be accepted, but even small changes are worthwhile and on their own can result in much increased insulin sensitivity wi thin weeks Full compliance may not be possible for the functionally or cognitively impaired, but an ex perienced dietician or nurse working with the patient and family is usually effective Severe dietary restrictions are often not appropriate, especially for the very old or very frail Beware the strict diet that takes enjoyment from (the last months of) life while giving little back Education \200 Educate family, carers, and nursing home staff continually \200 Provide simple written information and instructions \200 The approach must be tailored to the ind ividual, taking note of cognitive and sensory impairments Other interventions \200 Exercise, especially endurance exercise (eg walking, cycling) im proves insulin sensitivity Weight loss. Even modest reductions are bene \201 cial \200 Reduction of other vascular risk factors, including smoking \200 Home or pendant alarm systems in case of hypoglycaem ia DIABETES: TREATMENT 425 Disease surveillance Patients should be encouraged to take control of their own diabetic co ntrol and facilitated to monitor their own blood sugars. In addition they should be reviewe d at least annually. In the very frail or dependent, regular reviews remain vital, eg to en sure that treatments remain appropriate and that adverse effects have not occurred. \200 Assess diet/drug concordance \200 Check weight \200 Optimize cardiovascular risk factor s including blood pressure and lipids \200 Assess glycaemic control \200 Blood glucose testing, supplemented by 6-monthly HbA 1c estimation is the preferred method Urine glucose testing is less reliable, due to increased renal glucose threshold Examine for evidence of complications, including microalbuminuria, an early sign of nephropathy Ensure regular retinal screening is in place \200 Check feet and advise on their care (se e b \200\230The elderly foot \200\231, p.490) 2Utilize the advice and support of nursing s taff with specialist knowledge of diabetes \200\224 either community nurses with a special interest, or dedicated diabetes specialist nurses. 426 CHAPTER 15 Endocrinology Diabetes: oral drug treatment Biguanides For example: metformin (start at 500mg od) \200 Commonly used as \201 rst-line drug therapy in obese (BMI > 25), elderly patients (where insulin resistance predominates) Do not cause hypoglycaemia \200 Common side effects are nausea, diarrhea, anorexia, and w eight loss. These are less common if the drug is introduced slowly (500mg od, increased inc rementally each week to maximum 850mg tds) Can cause lactic acidosis in patients with hepatic or renal impairment, or where tissue hypoxia increases lactate production \200 Use cautiously in patients with kidney impairment (avoided if eGFR <30), hepatic impairment or heart failure (even if trea ted). Age itself is not a contraindication Stop in acutely unwell patients (especially with sepsis, respiratory failure, heart failure, or MI) Discontinue before anesthesia or the administration of radiographic contrast media, restarting if/when renal function normalizes Sulphonylureas For example: gliclazide (start at 40mg od) \200 Commonly used as \201 rs t-line drug therapy in lean elderly patients (where impairment in insulin release predominates) Can cause hypoglycaemia. This is uncommon if short-acting agents (gliclazide, glipizide, to lbutamide) are used. Avoid long-acting drugs (chlorpropamide, glibenclamide) which can caus e prolonged and damaging hypoglycaemia. In patients taking these (often for years without p roblems), consider a switch to shorter-acting drugs Commonly cause weight gain Thiazolidinediones For example: pioglitazone (start with 30mg od) \200 Effective in older people; do not cause hypoglycaemia. May be used: \200 As monotherapy, if intolerant of s ulphonylureas and biguanides \200 In combination with either a sulphonylurea or biguanide if control with that combination has been unsatisfactory Increasingly used as part of triple therapy to avoid introducing insulin LFTs must be monitored, initially 2-monthly. Stop if dysfunction occurs. Mild abnormalities at onset secondary to fatty liver are not a contraindication Can be used in mild/moderate renal failure. Avoid in heart failure. Doubles risk of bone fracture in women Pioglitazone has a more favorable cardiovascular risk pro \201 le DIABETES: ORAL DRUG TREATMENT 427 A -Glucosidase inhibitors For example: acarbose (start with 25mg bd twice daily, taken with the \201 rst mouthful of food) \200 Only moderately effective (HbA 1c reduction 0.5 \200\2231 % ), either as \201 rst-line or add-on therapy. Despite modest potency and side effects, they have a place, and may, eg, help delay or avoid the need for insulin Gastrointestinal side effects ( \202 atulence, bloating, diarrhea) usually settle with tim e and are less severe if the dose begins low and is increased slowly There are no severe side effects. Hypoglycaemia is never a problem HOW TO Manage older diabetic people in care homes In care homes: \200 The prevalence of diabetes is very high \200 Individual diabetic pa tients are at great risk of complications \200 Hypoglycaemia and other medication side ef fects are frequent To enhance quality of care: \200 Every resident should be screened for diabetes on admission to the home and each year thereafter. Blood sampling is far more sen sitive than urinalysis Every resident with diabetes should have an individual care plan including at least: diet, medications, glycaemic targets, and monitoring schedule. Monitori ng should be varied in time (pre-/post-prandial; breakfast, lunch, evening meal, late eveni ng), to provide a more complete picture of glycaemic control Diabetic diets should be available \200 An annual diabetes review should be performed by either a nurse with specialist training in diabetes, a GP, or a specialist (geriatrician or diabetologist) An annual ophthalmic screening assessment should be performed. Rarely, domiciliary screenin g is available. Usually, the resident will need to leave the home to attend a specialist sc reening center, but this is usually worthwhile as vision contributes signi \201 cantly to quality of life There should be easy access to specialist services including podiatry, optometry, diabetic foot clinic, dietetics, and diabetes specialist nursing Each home with diabetic residents should have a diabetes care policy. Staff should have rec eived training in the identi \201 cation and treatment of diabetic emergencies and the pre vention of complications Further reading Diabetes UK ( 2010 ). Good Clinical Practice Guidelines for Care Home Resid ents with Diabetes . London : Diabetes UK . 428 CHAPTER 15 Endocrinology Diabetes: insulin treatment \200 Insulin is essential for the treatment of type 1 diabete s \200 Insulin is started in type 2 diabetes when oral agents fail to achieve adequate control, if hyperglycaemia is severe (especially if the patient is lean, and insul in de \201 ciency likely), if a patient is unwell, and if oral drugs are contraindicated ( eg hepatorenal impairment) Side effects include: Weight gain . Common. Lessened if an oral drug (especially metformin) is co-prescribed Hypoglycaemia . Much more common with insulin than with any oral agent Insulin regimens \200 Increasingly initiate treatment with very long-acting insulins (ins ulin glargine and insulin detemir) which are effective if given just once daily. These are parti cularly helpful in those who: \200 Require assistance (relative, nurse) with injections \200 Are frequently hypoglycaemic on other regimens, especially at night \200 Would othe rwise need twice-daily insulin injections plus oral drugs \200 Alternative strategies, eg twice-daily insulin injections with pre-mixed insulins (eg Humalog Mix 25) are becoming \200\230old-fashioned \200\231. They are rarely initiated now but some older patients hav e been stable for years on such treatment so there is no advantage in changing Daily long-acting insulin once daily can be supplemented by oral hypoglycaemics during the day If eating is very erratic, consider giving short-acting insulin after each meal based on what has been eaten \200\224 a simple sliding scale Regimens based on rapid-acting insulin alone or a basal-bolus structure (the mainstay of ma nagement in younger patients with type 1 diabetes; provide an insulin pro \201 le as close to health as possible), are rarely appropriate in older people unless lifestyle (meals and activity) are especially chaotic and the patient has the cognitive and physical ability to manage dosing Initiating insulin \200 Involve the MDT (especially the diabetic nurse specialist) \200 If the patient is likely to need professional support to administer insulin, then also inv olve community teams \200\224 insulin administration may be very time-consuming for them Patients may be very reluctant to begin, because of fears about injections, hypos, or learning new skills Remember insulin administration issues: cognition, dexterity, and vision \200 Pre-mixed i nsulins avoid having to draw up multiple types of insulin \200 Insulin pens make the meas uring of doses much easier for patients, but syringes are more suitable when insulin is dra wn up by a third party (relative or nurse) In disposable pens, the vial is pre-loaded. This is helpful for patients who are not so dexterous DIABETES: INSULIN TREATMENT 429 Some patients are able to self-inject, but cannot safely draw up insulin into syringes or u se an insulin pen. In this case, doses may be drawn up in syringes by relatives or the comm unity nurse, and stored in a refrigerator until needed If insulin is given by a relative, what happens during family holidays? Changing insulin requirements \200 Always consider whether your patient is on the correct insulin regimen (type and dose) Earlier in the course of the disease, insulin requirements often rise as disease severity increases In advanced old age, insulin requirements often fall as appetite declines, body weight drop s, and renal function deteriorates. Type 2 diabetic patients on insulin may get off insulin altogether. Stop insulin, maximize oral drug treatment, and monitor regularly Dying patients can often have treatment withdrawn (see b \200\230HOW TO Manage diabetes in the terminally ill patient \200\231, p.434) Further reading European Diabetes Working Party for Older People . Clinical guidelines for type 2 diabetes mellitus . online: M http://www.eugms.org/index.php?pid=30 . 430 CHAPTER 15 Endocrinology Diabetes: complications In general, these are more common in older people, especially vascu lar complications. Evidence for risk reduction in very old diabetic patients is weak. In pr actice, evidence from younger age groups is extrapolated to apply to older groups, except i n the very frail and/or those with very poor life expectancy, where a more conservative app roach may be appropriate. Make an individual decision. Vascular A very common cause of morbidity and mortality. The risk of MI is as high in diabe tic patients without known coronary disease as it is in non-diabetic patients who have had an infarct. \200 Improve glycaemic control to the extent that it is possible without inducing hypoglycaemia Treat hypertension if it is persistent despite lifestyle management: \200 Target blood pr essure <140/<80mm Hg; lower if eye or kidney disease In the frail, target blood pressure <150/<90mm Hg \200 The drug class used is less import ant than the reduction in blood pressure achieved. B -blockers are not contraindicated. ACE inhibitors and ARBs may have an important additional effect in preventing nephropathy Treat hyperlipidaemia except in the very elderly and frail. Statins are well tolerated. The Heart Protection Study demonstrated bene \201 t in diabetic patients with cholesterol > 3 .5mmol Stop smoking. Health bene \201 ts begin in 3 \200\2236 months \200 Low-dose aspirin shou ld be offered to all older patients with diabetes (since 10-year coronary risk is > 15 % ) unless there is a contraindication. Control hypertension beforehand 2In older people, blood pressure control is as important as glycaemic control in reducing c ardiovascular risk. Neuropathy This is more common in older diabetic people and is often asymptomatic although may contribute to falls (see b \200\230Balance and dysequilibrium \200\231, p.112). Annual screening is necessary: check pinprick, vibration sense, light touch (nylon mono \201 lam ent), and re \202 exes. \200 Classically and most commonly a distal symmetrical polyneur opathy is seen. Consider other causes Mononeuropathy is usually of sudden onset, asymmetrical and resolves over weeks or months. Often painful. May coexist with polyneuropathy. For example: \200 Third nerve palsy. Most common. Causes ophthalmoplegia \200 Diabetic amyotrophy. Pelvic girdle and thigh muscle weakness and wasting. Dif \201 culty rising from chair Diabetic neuropathic cachexia. Painful peripheral neuropathy, depression, anorexia and weight loss Treatment is to exclude other causes, to optimize glycaemic control, to control pain, and t o support the patient through the illness, treating com- plications (eg depression) as they arise. DIABETES: COMPLICATIONS 431 Nephropathy A major problem in older diabetic people. \200 Microalbuminuria indicates a g roup at high risk of progression. Treat hypertension aggressively (preferentially with ACE inhibitors or ARBs), target BP 130/80 an d optimize glycaemic control If renal function deteriorates rapidly, exclude papillary necrosis by obtaining emergency renal tract ultrasound Eyes Retinopathy, glaucoma, and cataract are common (see b \200\230The eye and systemic di sease \200\231, p.579). All diabetic people should have annual screening ophthalmic assessm ent that includes retinal examination (fundoscopy via a dilated pupil) and visual acuity te sting. This is usually provided by ophthalmic specialist clinics or by diabetologists (or o ther physicians) with particular expertise. Indications for urgent referral for specialist assessment include: \200 Inadequacy of fundoscopic examination, eg due to cataract \200 Diabetic maculopathy. Either exudates close (<1 optic disc diameter) to the macula, or sus picion of macular oedema (nothing may be observed that is abnormal, but visual acuity is im paired) Preproliferative changes (many cotton wool spots, \202 ame or blot hemorrhages, venous change (beading, loops)) Proliferative changes (pre-retinal or vitreous hemorrhage new vessels, retinal detachment) 2Preventing blindness depends on early diagnosis of diabetes, good gly- caemic control, eff ective retinal screening, and early treatment of macu- lopathy and retinopathy. Ears Malignant otitis externa, manifesting as severe ear pain, is more common in diabetes ( see b \200\230Osteomyelitis \200\231, p.488). Teeth Gum disease and caries are more common. Good oral hygiene and regular dental assessme nt are essential. Feet Neuropathy and vascular disease lead to infection, injury, and ischaemia. Outcomes imm obility, and amputation. Impeccable foot care is essential (see b \200\230The elderly foot \200\231, p.490). include pain, ulceration, 432 CHAPTER 15 Endocrinology Diabetic emergencies Although overall presentations with diabetic emergencies are diminishi ng, two are especially important \200\224 hypoglycaemia and hyperosmolar non- ketotic stat e (HONK). However, older patients can present with any diabetic problem, including diabetic ketoacidosis. Hyperosmolar non-ketotic state \200 A complication of type 2 diabetes, and may be the \201 rst presentation \200 Most common in older people \200 Often severe. Mortality is very high (10 \200\22320 % ) \200 There is often underlying sepsis, particularly pneumoni a. Leucocytosis is common, with or without infection. Have a low clinical threshold to begi nning antibiotics, after blood and urine cultures There is usually enough endogenous insulin to suppress ketogenesis but not hepatic glucose output. Therefore there is usually only a mild metabolic acidosis (pH > 7.3), and ketonaemi a is absent or mild. Blood glucose is often very high ( > 30mmol/L) Subacute deterioration occurs. Impaired thirst and an impaired \200\230osmostat \200\231 c ontributing to severe dehydration with high serum osmolarity, hypernatraemia, and uraemia. The \202 uid de \201 cit is often around 10L Neurological problems are common and include delirium, coma, seizures, or focal signs, eg hemiparesis. Only a small proportion are in coma Treatment elements include: Fluid volume resuscitation . Frequent and careful clinical assessment and \202 uid prescr iption is usually suf \201 cient to determine rate and volume, but consider insertion of a central line in those with cardiac or renal disease or who are shocked. In general, \202 uid administration should be slower than in the younger patient with diabetic ketoacidosis . For the patient who is sick but not moribund, 2L in the \201 rst 3hr and a total of 3 \200\2234L in the \201 rst 12hr is often optimal. The exception is the shocked patient, w here \201 lling should be more aggressive, with the advice and support of ITU colleagues if appropriate Correction of electrolyte abnormalities . Initially give normal saline. If plasma sodium is very high ( > 155mmol/L) consider 5 % dextrose when sugars are under control (eg <12 mmol/ L). Maintain serum potassium in the range 4 \200\2235mmol/L. Give potassium with \202 uid even if the patient is normokalaemic, as patients are usually total body potassium-deplete d, and insulin will drive potassium into cells. Hypokalaemia is a major cause of dysrhythmi as and sudden cardiac death Hyperglycaemia often responds well to rehydration and treatment of an underlying cause (eg sepsis). Iv insulin is often needed, but modest doses (eg 1 \200\2233 units per hr) are usu ally enough. Patients with HONK are more insulin-sensitive than those with diabetic ketoaci dosis DIABETIC EMERGENCIES 433 Thromboprophylaxis . Low molecular weight heparin should always be prescribed; some advocat e full anticoagulation because the thromboembolic complication rate is very high Pressure care Although mortality rates are high, many patients recover promptly. The severity of presenta tion does not correlate closely with the severity of underlying disease, and in some, the d iabetes may subsequently be controlled with diet alone Hypoglycaemia Risk of severe hypoglycaemia increases hugely with age. In older people: \200 The physiological response to hypoglycaemia is weaker (eg reduced glucagon secretion) Autonomic warning symptoms (eg sweating, tremor) are less marked \200 Psychomotor respons e may be slow, even if symptoms are recognized Other risk factors include frailty, comorbid ity, renal impairment, care home residency, social isolation, and previous hypoglycaemia. C linical features are often not recognized or are atypical: Check a sugar in any unwell known diabetic person (eg falls, confusion) \200 Focal neurol ogical signs or symptoms may be misdiagnosed as stroke. Signs may persist for some time after correction of blood sugar \200 Acute severe or chro nic hypoglycaemia can cause a dementia-like syndrome Prevention \200 Assess each patient \200\231s risk of hypoglycaemia, and individualize th erapy \200 Balance the lifetime risk of hypoglycaemic attacks with reduction in long-term complications If altering medications, monitor sugars closely afterwards \200 Educate patient and carer s about signs and symptoms, and the therapeutic response Put in place alarm systems \200\224 pendant alarms, \200\230check \200\231 telephone call s, neighbor visits etc Accept higher target glucose levels for those at high risk Treatment \200 \200\230Hypos \200\231 can persist for hours or days and can recur late, especially if a long-acting insu lin or oral drug is responsible. If severe, monitor closely (if necessary by admission) for 2 \200\2233 days Post-event, explore why the \200\230hypo \200\231 occurred. How might the next be prevente d, or better treated? Many patients have lost weight or appetite and require a substantiall y reduced hypoglycaemic prescription 434 CHAPTER 15 Endocrinology HOW TO Manage diabetes in the terminally ill patient This includes end-of-life situations in all disease, not just cancer. The sole aim of therapy is to minimize symptoms of hypo- and hyperglycaemia. Ensure that family and carers understand the changed aims of treatment and the rationale for medication changes. Involve community nursing teams and diabetes specialist nursing teams early, particularly i f you are planning a discharge from hospital to home. Drug treatment \200 As weight declines and oral intake falls, lower doses of insulin and oral drugs are usually needed Dose reductions will also be needed as renal function declines \200 Make stepwise reducti ons in drug(s) and assess response \200 In some cases, drugs may be phased out completely . For example, type 2 patients on insulin may now manage on oral drugs alone; those on oral drugs may be asymptomatic off them Type 1 patients require insulin until the very latest stages of dying (eg coma). Simpli \201 cation of an insulin regimen (eg a move to once daily insulin) is often helpful, and m ay allow a patient to be cared for at home Diet Encourage food and \202 uid of whatever type is acceptable and attractive to the pat ient. Rigidly imposed diabetic diets are futile and unkind \200\224 it is usually better t o encourage food of whatever type can be taken, and to accept the (usually modest) conseque nces for glycaemic control. Blood glucose monitoring \200 Monitoring should be tailored to the individual patient. In general, testing can be relaxed In all cases, test if symptoms suggest hypo- or hyperglycaemia \200 In patients who are c linically stable (ie their condition is steady) or slowly deteriorating, testing can be inf requent (perhaps once on alternate days) In patients whose condition is deteriorating, or in those who have begun steroids, or where diabetes treatment has recently been changed, then testing should be more frequent In the patient who is moribund or comatose due to terminal illness, testing is pointless DIABETIC EMERGENCIES 435 HOW TO Interpret thyroid function tests See Table 15.1. \200 TSH is the most useful screening test. It can also be used to monito r treatment of thyroid disease. TSH takes 6 \200\2238 weeks to respond to changes in serum T3 and T4 so don \200\231t rush to repeat tests too often. If TSH is abnormal check free T4 Total thyroxine (total T4 and total T3) is affected by changes in thyroid binding globulin (TBG). Some drugs in \202 uence TBG, eg glucocorticoids, androgens decrease TBG levels whi le oestrogens, tamoxifen, and raloxifene increase TBG levels Free T4 (FT4) has replaced total thyroxine measurement in most centers as it is less in \202 uenced by changes in TBG Free T3 is useful to monitor thyrotoxicosis especially if T4 is not elevated with a suppressed TSH Table 15.1 Interpreting thyroid function tests TSH FT4/FT3 Most likely diagnosis Other causes Low High Hyperthyroidism, eg toxic nodule Graves \200\231 disease Thyroiditis Thyroxine overtreatment Post radio-iodine treatment Thyroxine overdosage Low Low Non-thyroidal illness Secondary/central hypothyroidism High Low Primary hypothyroidism Post-treatment (irradiation/ surgery) High Normal Subclinical hypothyroidism Recovery from non-thyroidal illness Poor compliance with thyroxine Certain drugs * High High Very rare TSH secreting tumor Assay error Variable compliance with thyroxine Certain drugs * Normal Low Secondary/central hypothyroidism Many common drugs cause abnormalities in TFT or change the effectiveness of treatment. 2Alw ays consult the BNF . 436 CHAPTER 15 Endocrinology Hypothyroidism: diagnosis Common: up to 5 % prevalence in older men, 15 % in older women. I ncidence increases with age. Causes Primary autoimmune disease (Hashimoto \200\231s disease, usually without goiter) is by far the most likely cause, unless iatrogenic causes are present (eg drugs (amiodarone, a ntithyroid drugs), previous hyperthyroidism treatment (radioiodine or surgery), head/neck r adiotherapy). Presentation \200 Onset is usually insidious: over months, years, or decades \200 Very variable presentation, often unmasked by intercurrent illness. In older people, symptoms an d signs are more often mild and non- speci \201 c. None or all of the following may occur: \200 Hypothermia, cold intolerance \200 Dry skin, thinning hair \200 Weight gain or loss, constipation \200 Malaise \200 Falls, immobility, weakness, myalgia, arthralgia, elevated CK \200 Bradycardia, heart failure, pleural or pericardial effusion, non-pitting 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