Oxford Handbook of General Practice (4 edn)
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Symptoms of endocrine disease
Hormones secreted by the endocrine system perform a wide range of functions. Therefore, clinical presentation of different endocrine disorders varies widely from non-specific symptoms such as tiredness, to very specific signs such as delayed puberty. Specific features depend on the gland and hormones involved.
Polydipsia
Over-frequent drinking of fluid—often associated, for logical reasons, with polyuria. Ask if associated with thirst. Take a history of fluid intake. If no history of excess fluid intake and BM/fasting blood glucose/HbA1c is normal, investigate further with U&E, Cr, and Ca2+.
Common causes
Change in lifestyle: diet/activity/exercise level—may be associated with polyuria but no other symptoms. No history of thirst
DM—usually accompanied by a history of thirst
Other causes
Diarrhoea, diabetes insipidus, ↑ Ca2+, compulsive water drinking (may be a feature of psychotic illness), phosphorus poisoning.
Polyuria
Passage of excessive urine. Check the patient does not mean frequency of urination. It can be difficult to distinguish the two. Causes are similar to those of polydipsia and the 2 symptoms are related. Take a history of fluid intake. If no history of excess fluid intake and BM/fasting blood glucose/HbA1c is normal, investigate further with MSU (for M,C&S), U&E, Cr, and Ca2+.
Consider
DM—always check a BM and/or fasting blood glucose if a patient complains of polyuria
Diabetes insipidus
Hypercalcaemia
Excessive intake—due to change in lifestyle or psychiatric conditions, e.g. schizophrenia
Chronic renal failure
Drugs—diuretics, caffeine, alcohol
Glycosuria
Often detected incidentally on urine dipstick. Causes:
DM
Pregnancy
Sepsis
Renal tubular damage
Low renal threshold
In all cases, check HbA1c/fasting blood glucose (+ glucose tolerance test if pregnant). Check immediate BM if other symptoms suggestive of DM.
Hirsutism
Affects 10% ♀. Excess hair in androgenic distribution. Causes:
Most cases are idiopathic; there may be a family history
Drugs—phenytoin; corticosteroids; ciclosporin; androgenic oral contraception; anabolic steroids; minoxidil; diazoxide
Polycystic ovarian syndrome (PCOS)
Late-onset congenital adrenal hyperplasia (rare)
Cushing’s syndrome
Ovarian tumours (rare)
Assessment
History Long-standing or recent onset, family history, ethnic origin (more common in Mediterranean countries), menstrual history
Examination Distribution of excess hair
Investigation
Women with longstanding hirsutism (since puberty) and regular periods need no further investigation unless abnormal signs.
Otherwise: blood—testosterone (↑ in PCOS, androgen-secreting tumour, late-onset congenital adrenal hyperplasia); LH/FSH ratio (>3:1 suggests PCOS).
Refer to gynaecologist or endocrinologist if
recent onset, abnormal blood tests, virilism, galactorrhoea, menstrual disturbance, infertility, and/or pelvic mass.
Treatment of idiopathic hirsutism
Cosmetic—bleaching, shaving, waxing, depilatory creams, electrolysis
Weight ↓ in obese individuals
Psychological support
Topical eflornithine ↓ growth of unwanted facial hair. Continuous use for >8wk is required before benefit is seen. Must be used indefinitely to prevent regrowth. Discontinue if no improvement in 4mo
Oral medication—all must be taken for ≥6mo to take effect and none abolishes the problem. In all cases, continue treatment until acceptable level of hair growth then stop. Relapse usually follows withdrawal and repeat courses are then required. Drugs used: COC pill containing desogestrel or co-cyprindiol; spironolactone
Menopause
p. 710
Delayed or precocious puberty
p. 893
Obesity
p. 178
Metabolic syndrome (syndrome X; insulin resistance syndrome)
Impaired glucose tolerance or DM, insulin resistance (in patients on insulin, suggested by insulin doses >1u/kg/d) + other risk factors for CVD including:
Truncal obesity—waist circumference >0.9m (♀); >1.0m (♂), use 0.1m lower figures for people of south Asian extraction
↑ BP—>135/80
Dyslipidaemia—serum HDL <1.2mmol/L (♀) or <1.0 (♂); fasting serum triglycerides >1.8mmol/L
Associated with high risk of CVD. Treat risk factors aggressively.
Tiredness and lethargy
p. 528
Diabetes mellitus
Diabetes mellitus (DM) is a common syndrome caused by lack, or ↓ effectiveness, of endogenous insulin. It affects 3% of the UK population and is characterized by ↑ blood sugars + abnormalities of carbohydrate/lipid metabolism.
Classification of primary diabetes
Type 1
Occurs at any age but more common in those aged <30y. Autoimmune disease—islet cell antibodies may initially be present. Associated with other autoimmune disease and certain genotypes (HLA DR3/4—although identical twin concordance ≈30%.). Patients are prone to profound weight ↓ and ketoacidosis. Insulin is needed from diagnosis.
Type 2
80–90% patients with DM. ♂:♀≈ 3:2. Prevalence is rising. Lifetime risk of developing type 2 DM is >10% and ∼50% remain undiagnosed. Risk factors:
Age >65
Obesity
FH of DM (identical twin concordance ≈ 100%)
Impaired glucose tolerance
Ethnic group—South Asians/Afro-Caribbeans have 5–10x ↑ risk
PMH of gestational diabetes or a baby >4kg at birth
Progressive disease resulting from impaired insulin secretion and insulin resistance. Life expectancy is ↓ by 30–40% in the age range 40–70y—a ↓ of 8–10y of life. Onset is often insidious; 50% have complications at diagnosis.
Latent autoimmune diabetes in adulthood (LADA)
6–10% of patients with type 2 DM. Characterized by anti-glutamic acid decarboxylase (GAD) antibodies. Associated with higher risk of ketoacidosis and ↑ risk of progression to insulin dependence. Suspect if type 2 DM and:
Absence of metabolic syndrome features
Uncontrolled hyperglycaemia despite oral agents, and/or
Other autoimmune diseases (e.g. thyroid disease, pernicious anaemia)
Maturity onset diabetes of the young (MODY)
1–2% of patients with DM. Present <25y and there is a family history. Genetic syndrome with autosomal dominant inheritance. Gene mutations involved: HNF1-α (70%); HNF1-β; HNF4-α; glucokinase. Gene testing is important to identify the type of MODY, as treatment differs according to type.
Diabetes and pregnancy
p. 828
Other (secondary) causes of DM
Drugs Steroids, thiazides
Pancreatic disease Pancreatitis, surgery, pancreatic cancer, haemochromatosis, cystic fibrosis
Endocrine disease Cushing’s disease, acromegaly, thyrotoxicosis, phaeochromocytoma
Others Glycogen storage diseases, insulin receptor antibodies
Blood glucose may be temporarily ↑ during acute illness, after trauma or surgery or during short courses of blood glucose-raising drugs (see 2° causes). If HbA1c >48mmol/mol DM is likely.
Presentation
Acute Ketoacidosis or hyperosmolar non-ketotic coma ( p. 1100)
Subacute Weight ↓, polydipsia, polyuria, lethargy, irritability, infections (candidiasis, skin infection, recurrent infections slow to clear), genital itching, blurred vision, tingling in hands/feet
Asymptomatic Incidental finding or through risk stratification
Risk stratificationN
Use a risk stratification tool (e.g. Diabetes Risk Score or QDiabetes) to assess all patients:
>40y, or
>25y of South Asian, Chinese, Afro-Caribbean, or black African origin, from hard-to-reach populations (e.g. homeless) or with other medical conditions that predispose to DM (e.g. pancreatitis)
If low/intermediate risk, give lifestyle advice and reassess in 5y. If high risk or of South Asian/Chinese ethnic origin and BMI >23kg/m2, check FBG or HbA1c:
FBG <5.5mmol/L or HbA1c <42mmol/mol—provide lifestyle advice and reassess every 3y
FBG 5.5–6.9mmol/L or HbA1c 42–47mmol/mol—provide interventions to ↓ risk (e.g. weight management, dietary advice, help with smoking cessation, BP and lipid management) and reassess annually
FBG ≥7.0mmol/L or HbA1c ≥48mmol/mol—consider type 2 DM
Diagnosis of diabetes
If symptomatic
↑ plasma glucose (random ≥11.1mmol/L; fasting ≥7.0mmol/L) or ↑ HbA1c ≥48mmol/mol. For all children and adults with suspected ketoacidosis or who are unwell, do not delay to get a laboratory sample, but admit or refer for same-day specialist assessment on BM alone. Otherwise only diagnose with laboratory samples.
If asymptomatic
↑ plasma glucose (random ≥11.1mmol/L; fasting ≥7.0mmol/L) or ↑ HbA1c ≥48mmol/mol on two separate measurements on different days
↑ plasma glucose (random ≥11.1mmol/L; fasting ≥7.0mmol/L) and ↑ HbA1c ≥48 mmol/mol at the same testing
Pre-diabetes (non-diabetic hyperglycaemia)
FBG ≥6.1 and <7mmol/L or HbA1c of 42–47mmol/mol. Risk factor for DM and CVD. Follow-up with annual FBG or HbA1c. 4%/y develop DM. Treat CVD risk factors aggressively.
Further information
WHO Use of glycated haemoglobin (HbA1c) in the diagnosis of diabetes mellitus (2011) 
www.who.int/diabetes
NICE www.nice.org.uk
Type 1 diabetes: diagnosis and management (2004)
Preventing type 2 diabetes: risk identification and interventions for individuals at high risk (2012)
Patient advice and support
Diabetes UK 
0845 120 2960 www.diabetes.org.uk
Organization and monitoring of care
Aims of diabetic care
Alleviation of symptoms
Minimization of complications
↓ in early mortality
Quality of life enhancement
Education of the patient and family/carers
Features of well-organized care
Use of a register and structured records (available as part of in-house computer software)
6-monthly review, with recall system and follow-up of defaulters
Protocol for patient-centred care, including provision of personal care plans tailored to each individual and including self-management plans
Provision of protected time for the clinic
Availability of good quality written information for patients
Open access for patients to receive advice
Multidisciplinary team covering all aspects of diabetes care—GPs, diabetes nurse specialists/assistants, educators, dieticians, and podiatrists
Quality monitoring through audit and patient feedback
Continuing education for professional staff
Routine diabetic review
Each diabetic patient requires 6-monthly review (or more frequent, as necessary). This should include a thorough annual review of all aspects of disease and care. Reviews should cover:
Problems Recent life events; new symptoms; difficulties with management since last visit
Review of:
Indices of control, e.g. HbA1c
Self-monitored results and discussion of their meaning
Lifestyle—dietary behaviours; physical activity; smoking
Diabetes education—including referral to a structured education programme for those newly diagnosed and information on lifestyle, self-care, support, and when to step up treatment/seek further medical help
Skills, e.g. injection technique
Foot care
Blood glucose, lipid and BP therapy, and results
Other medical conditions and therapy affecting DM
Immunizations—influenza ± pneumococcal vaccination
Depression screening ( p. 199)
Review of complications Annual review—more frequent if established complications. Cardiovascular disease; nephropathy; neuropathy; eye disease; foot problems; erectile dysfunction
Review of services Annual review—more frequent if problems
Analysis and planning Agreement on the main points covered, targets for coming months, changes in therapy, interval to next review
Recording Completion of structured record ± patient-held record
7–10% of patients in long-term residential care have DM. Patients in residential care with DM tend to be neglected. Agree a diabetes care plan for each affected resident, and ensure at least annual diabetic review.
Monitoring blood glucose
All patients can achieve good levels of control (see Table 12.1). Poorer control is acceptable in the elderly or others with limited life expectancy as long as they are symptom-free.
Fingerprick capillary glucose monitoring Essential for all patients using insulin. Useful for patients taking sulfonylureas/glinides
Explain the range of suitable monitoring devices available (BNF 6.1.6), and train in the use of the selected method
Frequency of self-monitoring varies according to need
Set targets for preprandial glucose levels
Assess skills (and meters) yearly or if problems self-monitoring
Evaluate reliability of results by comparison with HbA1c results and results obtained at review
Glycosylated haemoglobin (HbA1c) Measure at least 2x/y. Represents average blood glucose control over the previous 6–8wk
| Measure | Target |
|---|---|
Blood glucose (mmol/L) | 4–7 fasting (post-prandial <9)—adults 4–8 fasting (post-prandial <10)—children |
Urine | −ve (postprandial sugars <0.5%) |
HbA1c (normal 20–42 mmol/mol)—measure every 2–6mo depending on control | 48–58mmol/mol* If HbA1c remains high but pre-meal self-monitoring levels remain well controlled (<7.0mmol/L), consider self-monitoring to detect postprandial hyperglycaemia (>8.5mmol/L). |
Serum cholesterol (mmol/L) | ↓ total cholesterol by 25% or to <4—whichever is the lower value or ↓ LDL cholesterol by 30% or to <2—whichever is the lower value |
BMI (kg/m2) | 25–30 |
BP (mmHg) | <140/80—uncomplicated type 2 DM <135/85—uncomplicated type 2 DM <130/80—if any renal, foot, eye or cardiovascular complications of type 1 or type 2 DM |
| Measure | Target |
|---|---|
Blood glucose (mmol/L) | 4–7 fasting (post-prandial <9)—adults 4–8 fasting (post-prandial <10)—children |
Urine | −ve (postprandial sugars <0.5%) |
HbA1c (normal 20–42 mmol/mol)—measure every 2–6mo depending on control | 48–58mmol/mol* If HbA1c remains high but pre-meal self-monitoring levels remain well controlled (<7.0mmol/L), consider self-monitoring to detect postprandial hyperglycaemia (>8.5mmol/L). |
Serum cholesterol (mmol/L) | ↓ total cholesterol by 25% or to <4—whichever is the lower value or ↓ LDL cholesterol by 30% or to <2—whichever is the lower value |
BMI (kg/m2) | 25–30 |
BP (mmHg) | <140/80—uncomplicated type 2 DM <135/85—uncomplicated type 2 DM <130/80—if any renal, foot, eye or cardiovascular complications of type 1 or type 2 DM |
Adjust target to the individual.
Patients with type 2 DM who have a Group 2 driving licence and are taking sulfonylureas or glinides must check blood glucose twice daily so will need blood glucose meters and a supply of testing sticks.
Further information
NICE Diabetes in adults quality standards (2011) www.nice.org.uk
Management of diabetes: education
Education is an essential aspect of diabetic care. Diabetes is a chronic condition, and however well it is managed in the clinic, the patient has to manage his or her own disease the rest of the time. Everyone with DM should receive education through a structured, quality-controlled education programme, e.g. diabetes education and self-management for ongoing and newly diagnosed (DESMOND). Education enables patients and their carers to become equal partners in the management of their disease. Topics to cover during routine reviews:
General knowledge
Information about:
DM, its progressive nature, and complications
Aims of management
Structure of diabetic services and ways to access them
Equipment required and usage instructions—syringes, needles, blood testing equipment, etc.
Free prescriptions for patients requiring drugs or insulin to control their diabetes
Problems of pregnancy (women of childbearing age only)
Alert bracelets/tags—Medic-Alert ( 0800 581 420) or Medi-Tag ( 0121 200 1616) provide engraved jewellery, watches, and tags
Diet
Patients do not need a separate diet from the rest of the family or expensive ‘diabetes’ food products. A diabetic diet is a healthy diet.
Aim for ≥50% of calorie intake from fibre-rich carbohydrate, with minimum fat (especially saturated), refined carbohydrate, and alcohol
Adjust total calorie intake according to desired BMI
Recommend ≥5 portions of fresh fruit or vegetables/d
Spread food intake evenly across the day for patients controlled with tablets or diet
Diet sheets are available from Diabetes UK and should be provided
Ready-made meals, processed foods, and alcohol are often sources of hidden sugar
Immunizations
Offer influenza and pneumococcal vaccine to all patients with diabetes.
Psychological problems
Discuss concerns about the diagnosis of DM or development of complications. Arrange counselling/refer to self-help resources as needed. Teenagers with diabetes can be a particularly difficult group to manage. Often control is poor due to a combination of rapid bodily changes and rebellion against the diagnosis of DM. Support information and advice given in specialist clinics.
Exercise
Encourage regular exercise.
Review activity at work and in getting to and from the workplace, hobbies, and physical activity in the home
Advise physical activity can ↑ insulin sensitivity, ↓ BP, and improve blood lipid control
If appropriate, suggest regular physical activity tailored to individual ability (e.g. brisk walking for 30min/d; exercise prescription)
Smoking
Advice on and assistance with smoking cessation ( p. 182).
Driving
Advise all drivers that they must notify their car insurance company and the DVLA, unless their diabetes is controlled by diet alone. Be aware of insurers who cater for diabetic drivers.
Type 1 DM—must be aware of hypoglycaemic episodes
All type 1 DM and those with type 2 DM taking sulfonylurea or glinide: group 1 licence—<2 hypoglycaemic episodes/y requiring assistance of another person; group 2 licence—no hypoglycaemic episodes requiring assistance of another person and must monitor blood glucose 2x/d
Foot care
p. 360
Employment
Advise those on insulin that certain jobs are no longer possible:
Working on scaffolding or with dangerous machinery
Joining the police or the armed services
Driving a heavy goods or public service vehicle
Jobs without these hazards should pose no problems though the patient might wish to tell his/her employer. Special advice may be needed for shift work.
Travel
Give advice on:
Management of change in time zones ( p. 133)
Transport of insulin
Keeping monitoring and injection equipment in hand-luggage
Differences in insulin types and concentrations between countries
Travel related illness (especially gastroenteritis)
Need for immunization and travel insurance
Be aware of insurers who cater for diabetic travellers.
Further information
DH Structured patient education in diabetes: report from the Patient Education Working Group (2005) www.dh.gov.uk
NICE www.nice.org.uk
Patient advice and support
Diabetes UK 0845 120 2960 www.diabetes.org.uk
Treatment of type 2 diabetes
Always combine treatment of hyperglycaemia with modification of other risk factors for vascular complications— p. 354.
Healthy eating and exercise
Diet is the cornerstone of treatment. Diet sheets are available from Diabetes UK. ↑ physical activity is beneficial (↓ weight, ↓ lipids, and ↑ insulin sensitivity) but not always possible.
First-line oral hypoglycaemic agentsN
See Figure 12.1 and BNF 6.1.2.
Using oral hypoglycaemic agents in type 2 DM (HbA1c units are in mmol/mol)N
Biguanides
Metformin 500mg–1g bd. ↓ gluconeogenesis and ↑ peripheral utilization of glucose. Only effective if some endogenous insulin production. Initiate metformin for all patients if HbA1c remains ≥48mmol/mol after a trial of diet/lifestyle interventions. Avoid in very elderly patients and those with serious heart disease, liver/renal failure, or high alcohol intake, as ↑ risk of lactic acidosis. Hypoglycaemia is not a problem. Start with the minimum dose and ↑ monthly until control is achieved/maximum dose reached.
Sulfonylureas
(e.g. gliclazide 80–160mg bd) Consider first-line if not overweight, hyperglycaemic symptoms requiring rapid response, and/or metformin is contraindicated/not tolerated. Augment insulin secretion, so only effective if residual endogenous insulin production. All are equally effective. If one sulfonylurea does not work—another is not likely to either. Advise patients to take before meals—warn about hypoglycaemia if meals are omitted (and need for blood monitoring if group 2 driving licence). Start at the minimum dose, and ↑ until blood sugar is controlled/maximum dose is reached. Wait ≥1mo between adjustments. Main side effect is weight ↑.
Second-/third-line oral hypoglycaemic agentsN
(BNF 6.1.2)
Pioglitazone
15mg od. ↑ insulin secretion/sensitivity, slightly ↓ BP, and ↓ total cholesterol. Does not cause hypoglycaemia. May cause weight ↑. Use in combination with metformin and/or sulfonylurea for patients with poor glycaemic control. Associated with ↑ risk of bladder cancer, fluid retention, and heart failure.
DPP-4 inhibitors
(e.g. sitagliptin 100mg od, saxagliptin 5mg od, vildagliptin 5mg od/bd, linagliptin 5mg od) ↑ incretin levels. Do not cause weight ↑ or hypoglycaemia. Use with metformin and/or sulfonylurea if poor glycaemic control. Linagliptin is useful for patients with renal failure as excreted via the gall bladder.
Other treatmentsN
Exenetide (bd/weekly injection), lixisenatide (od injection) and liraglutide (od injection)—may be an alternative to insulin in obese patients. Stimulate insulin production and ↓ rate of glucose absorption from the gut. Licensed for use in addition to metformin and/or a sulfonylurea. Continue after 6mo only if HbA1c has ↓ >1mmol/mol and weight ↓ is >3% of initial body weight
Rapid-acting insulin secretagogues (nateglinide, repaglinide)—stimulate insulin release. Rapid onset and short duration of activity. May be useful as second-line treatment with metformin for those with erratic lifestyle
Starting insulin
( p. 352) If on dual therapy (metformin + sulfonylurea) and markedly hyperglycaemic, start insulin in preference to adding other drugs unless very good reasons not to. Continue metformin and sulfonylurea except if planning pregnancy. Review the use of sulfonylurea if hypoglycaemia occurs.
Drug treatment of obesity
p. 179.
Further information
NICE Type 2 diabetes (2009) www.nice.org.uk
Treatment with insulin
First-line treatment for type 1 DM and used when diet + oral therapy have failed for type 2 DM. Local guidelines govern who does what.
All drivers must notify the DVLA and their insurance company.
Types of insulin
Rapid-acting analogues (e.g. insulin lispro—fastest acting; peak 0–3h after injection; last 2–5h; give just prior to meals)
Soluble (clear) human, porcine, or bovine (e.g. Actrapid®—short-acting; peak 2–6h after injection; last 8h; give 15–30min before meals)
Intermediate- or longer-acting (cloudy) human, porcine, or bovine (e.g. Humulin I®)—peak 4–12h after injection; last up to 30h. Taken alone, od/bd to provide background insulin, or with short/rapid-acting insulin
Long-acting insulin analogues (e.g. insulin glargine)—last 24h; provide background insulin; as no peak, associated with ↓ risk of hypoglycaemia
Pre-mixed—combination of short- + long-acting insulin, e.g. 30%:70%
Examples of injection regimes*
Intermediate ± short-acting insulin od/bd (mane ± pre-evening meal)
Short- + intermediate-acting insulin mane, short-rapid-acting* insulin before evening meal, and intermediate-acting insulin before bed
Short-rapid-acting* insulin tds pre-meals + intermediate-acting pre-bed
Combinations of oral therapy + od/bd long-intermediate-acting insulin
Rarely, continuous sc infusion of short-acting insulin is needed to achieve control—needs specialist supervision
Administration
Deep sc injection into upper arm, thigh, buttock, or abdomen
Fat hypertrophy/scarring are minimized by rotation of injection sites
‘Pen’ devices and syringe/needle are equally effective. In all cases prime the needle using an ‘air shot’ (an empty needle ↓ insulin dose by ~2u)
Rock ‘pens’ containing premixed insulins to mix contents before use
↑ absorption can occur if a limb is exercised following injection
Monitoring
Check blood glucose pre-prandially ≥1x/d at different times—more often if multiple injection regimes, after dose changes or during intercurrent illness; ask patients to keep a timed/dated diary of readings
Record episodes of hypoglycaemia
Target: blood glucose 4–7mmol/L pre-meals, with hypoglycaemic episodes kept to a minimum (4–8mmol/L pre-meals if <18y old)
Starting insulin for patients with type 2 DM
Use a structured programme. Appropriate training is needed for all practice staff involved.
Before starting—teach home blood glucose monitoring; reinforce diet
Continue metformin ± sulfonylurea
Teach insulin injection technique—start 10u of long-acting insulin od
Teach patients/carers about safe disposal of sharps and hypoglycaemia
Give instructions to ↑ dose every 3–7d until target levels are reached e.g. average fasting glucose >10mmol/L—↑ by 6–8u/d; 8–10mmol/L—↑ by 4–6u/d; 6–8mmol/L—↑ by 2–4u/d
Provide a contact telephone number for advice; follow up after 2–3d and then as needed; check HbA1c every 3mo until stable
Exercise
↓ insulin dose acting at the time of exercise or take 1–2 glucose tablets before exercise, then check blood glucose afterwards. Adjust alterations/glucose dose with experience of effects of exercise.
Intercurrent illness
Continue insulin in usual dose and keep a regular check (≥qds) of blood sugar. Maintain glucose intake even if not eating (e.g. with Lucozade or milk).
If glucose >13mmol/L, ↑ insulin by 2u/d until control is achieved or use top-up injections of short-acting insulin qds prn
Admit to hospital if: condition warrants admission; unable to take glucose; persistent vomiting and/or dehydration; ketotic (check urine if blood sugar >13mmol/L)
Poor control
Exclude intercurrent illness
Consider psychosocial factors
Consider diet and/or gastroparesis
Check insulin is being used correctly
Check injection sites are not scarred or hypertrophic
Consider changing insulin dose—ask the patient to record a glucose profile (blood sugar pre-meals and before bed); if using >1 insulin, adjust one at a time ↑ or ↓ as needed; alter by ≤10% each time; allow ≥48h between dose adjustments; alter dose of insulin acting at the time blood sugar is most out of control
Hypoglycaemia
Emergency management
p. 1100
Advice for patients
Check blood sugar before driving and every 2h during a long journey
Carry glucose everywhere and sandwiches on long journeys
If hypoglycaemia occurs, stop hazardous activities and take action
Wait until fully recovered before resuming activities
In case of severe hypoglycaemia
Supply a responsible member of the family with glucose gel (e.g. GlucoGel®) and glucagon injection—teach him/her to use it. Response is short-lived—give oral glucose (e.g. Lucozade, glucose tablets, milk) as soon as the patient is conscious.
Recurrent hypoglycaemia
If hypoglycaemia occurs in a regular pattern check pattern of meals and activity and alter insulin to match needs
If erratic consider erratic lifestyle, alcohol, problems with absorption, errors in administration, gastroparesis
If no obvious cause, consider change in underlying insulin sensitivity (e.g. age, renal impairment)
Hypoglycaemia unawareness
To restore warning signs adjust insulin/food intake to stop glucose levels dropping to <4mmol/L. Consider undetected night-time hypoglycaemia if HbA1c < expected from blood sugar diary. Driving is not permitted if hypoglycaemic awareness has been lost or >1 hypoglycaemic episode requiring assistance from another individual in the past year (no episodes permitted for group 2 licence).
Diabetic complications: cardiovascular
Diabetic patients are at ↑ risk of MI (2–5x), stroke (2–3x), and peripheral vascular disease. Protective effect of female sex is lost. Atherosclerotic disease accounts for most of the excess mortality due to DM. Check arterial risk factors annually:
Age
Family history of arterial disease
Abdominal adiposity
BP
Lipid profile (LDL, HDL cholesterol, and triglycerides)
Albumin excretion rate
Blood glucose control
Smoking—give smoking cessation advice at every opportunity. Help patients who want to give up with advice, medication, and support
High-risk groups Consider patients at increased risk if:
>35y
Originate in the Indian subcontinent
Family history of premature heart disease
Pre-existing CVD
≥2 features of the metabolic syndrome ( p. 343)
Abnormal lipids
↑ BP
Microalbuminuria/proteinuria
Consider to be at high CVD risk unless all the following apply:
Not overweight for ethnic group
Normotensive (BP <140/80mmHg without antihypertensive therapy)
No microalbuminuria
Non-smoker
No high-risk lipid profile
No history of cardiovascular disease
No family history of cardiovascular disease
Aspirin
Control systolic BP to <145/90mmHg before starting treatment. Give 75mg od to all those with a prior history of CVD. Do not use for primary prevention.
Statin
Give a statin (e.g. simvastatin or atorvastatin) to:
All type 1 diabetics with ↑ risk of arterial disease
All type 2 diabetics aged >75y
Type 2 diabetics of any age with any high-risk factors
Type 2 diabetics >40y with no high risk factors, but who have 10y CVD risk >20%, calculated using special diabetic risk tables, e.g. UKPDS risk engine ( www.dtu.ox.ac.uk/riskengine)
Choice of statin depends on cost and other medication the patient is taking. Start with a mid-range dose (e.g. simvastatin 40mg or atorvastatin 20mg nocte). Recheck lipid profile 1–3mo after starting treatment. Aim to ↓ total cholesterol to <4mmol/L or ↓ LDL cholesterol to <2.0mmol/L. If treatment does not bring lipids within target levels, ↑ the statin dose or change to an alternative statin ( simvastatin at a dose of 80mg is no longer recommended; avoid 40mg dose in combination with amlodipine, diltiazem, verapamil, or amiodarone).
Triglycerides
If triglycerides are >4.5mmol/L despite optimal glycaemic control, start a fibrate (e.g. fenofibrate) to ↓ risk of pancreatitis. If this is ineffective, consider a trial of high-concentration omega-3 fish oils
If high CVD risk and triglycerides are 2.3–4.5mmol/L despite statin treatment, consider adding a fibrate
Blood glucose
Target HbA1c is <48mmol/mol if type 1 DM or type 2 DM treated with lifestyle measures or one/two oral agents. Otherwise target HbA1c is <58mmol/mol.
BP
Any ↓ in average BP ↓ risk of cardiovascular complications. Measure BP annually if not hypertensive and no renal disease. If BP is higher than target, consider 24h ambulatory blood pressure monitoring ( p. 246).
Type 1 DM N Treat if systolic BP >135 or diastolic BP >85mmHg, unless microalbuminuria/proteinuria or ≥2 features of the metabolic syndrome ( p. 343) when treat if systolic BP >130 or diastolic BP >80mmHg
Type 2 DM N Treat if systolic BP ≥140 or diastolic BP ≥80mmHg, regardless of absolute risk of CVD. Aim to ↓ BP to <140/80mmHg (or <130/80mmHg if kidney, eye, or cardiovascular disease)
Choice of antihypertensiveN
In all cases, discuss lifestyle modifications ( p. 249)
If already on antihypertensives at the time of diagnosis of DM, review BP and medication use. Change only if BP is poorly controlled or current medication is inappropriate
For those with new hypertension, start with an ACE inhibitor (unless possibility of becoming pregnant when start with Ca2+ channel blocker). Titrate dose to the maximum tolerated. If side effects with ACE inhibitor, ARB is an alternative. For people of Afro-Caribbean descent offer ACE inhibitor + Ca2+ channel blocker. Monitor BP every 1–2mo until stable within target
If BP remains above target add a calcium channel blocker (e.g. amlodipine 5mg od)
If BP still remains above target, add a diuretic (e.g. indapamide M/R 1.5mg od)
Fourth-line agents include alpha-blockers, beta-blockers, or further diuretic therapy, e.g. spironolactone 25mg od. Consider referral
Monitoring
Monitor BP every 4–6mo once stable on treatment. Check for possible adverse side effects of medication (including postural drop).
Further information
NICE www.nice.org.uk
Type 1 diabetes: diagnosis and management (2004)
Hypertension in adults (2011)
Diabetic complications: renal and eye
Renal disease
Urinary tract infections
More common in patients with poorly controlled DM. May exacerbate renal failure and lead to renal scarring. Consider papillary necrosis if recurrent (more common in DM).
Nephropathy
Most common cause of end-stage renal failure in adults starting dialysis in the UK. 25% diabetics have renal damage—more common if of Asian or African ethnic origin
Nephropathy is characterized by proteinuria, ↑ BP, and progressive ↓ in renal function
Before overt nephropathy occurs, there is a phase (microalbuminuria or incipient nephropathy) in which the urine contains traces of protein not detected by standard protein dipstick. Presence of ↑ urine albumin levels and/or ↑ serum creatinine is associated with ↑ risk of premature cardiovascular events and renal failure
Check renal function annually (first-pass urine specimen for albumin:creatinine ratio; dipstick for protein and haematuria; serum creatinine and eGFR)
Interpretation of albumin:creatinine ratio
Microalbuminuria is defined as albumin:creatinine ratio ≥2.5mg/mmol (♂) or ≥3.5mg/mmol (♀) or albumin concentration ≥20mg/L in the absence of overt proteinuria or urinary tract infection
If albumin:creatinine ratio is abnormal, repeat the test 2x over the next 3–4mo. Microalbuminuria is confirmed if ≥1 of the repeat results is also abnormal
Suspect other renal disease if
Albumin:creatinine ratio is ↑ without retinopathy
BP is particularly high or resistant to treatment
Heavy proteinuria (albumin:creatinine ratio >100mg/mmol) but previously documented as normal
Significant haematuria
GFR has worsened rapidly
The person is systemically unwell
Management of nephropathy
Optimize blood glucose control
Monitor and treat ↑ BP (target BP <130/80mmHg) and treat other arterial risk factors aggressively
Modify diet (↓ salt intake, ↓ protein intake with target of 0.8g/kg)
Treat all patients with DM and microalbuminuria or CKD with an ACE inhibitor (or ARB), titrating the dose to the maximum tolerated. This protects renal function and ↓ proteinuria, even if the patient is not hypertensive
Refer to a nephrologist if proteinuria (albumin:creatinine ratio >70mg/mmol, or total protein:creatinine ratio >100mg/mmol, and UTI excluded); eGFR <30 or eGFR drops by >15% between tests (see CKD p. 440)
Eye disease
∼1:3 diabetics have eye problems at the time of diagnosis.
Blurred vision
May occur if blood glucose control is poor—caused by osmotic changes in the lens, and corrects with normalization of blood sugar. Wait before changing glasses.
Cataract
Juvenile ‘snowflake’ cataracts are more common and can develop rapidly (over days). Senile cataracts occur ∼10y earlier in DM.
Glaucoma
DM is a risk factor for developing glaucoma.
Retinopathy
Most common cause of blindness in people of working age in industrialized countries (risk is ↑ x20 compared to non-diabetics). 20–40% type 2 diabetics have retinopathy at diagnosis. 20y after diagnosis, 95% type 1 diabetics and 60% type 2 diabetics have retinopathy—sight-threatening in 5–10%.
Pathogenesis of retinopathy
Small retinal blood vessels become blocked, swollen (aneurysms) or leaky causing exudate formation, oedema or new vessels. Laser treatment (photo-coagulation) halts progression but does not restore vision.
Good diabetic control slows development of retinopathy. Aim for HbA1c of <58 mmol/mol
Monitor and treat risk factors—BP, lipids (hard exudates), smoking
Fenofibrate ↓ risk of retinopathy and retinopathy progressionR. Place in routine management is yet to be determined
Digital retinal photography is available throughout the UK. Screen at least annually to detect retinopathy before visual loss occurs.
Refer to ophthalmologist if
Sudden loss of vision—E
Rubeosis iridis—E
Pre-retinal or vitreous haemorrhage—E
Retinal detachment—E
New vessel formation—U
Maculopathy—R
Pre-proliferative retinopathy—R
Cataract affecting visual acuity—R
Unexplained drop in visual acuity—R
E = Emergency; U = urgent; R = routine
Further information
NICE www.nice.org.uk
Type 1 diabetes: diagnosis and management (2004)
ACCORD Study Group and ACCORD Eye Study Group (
Diabetic complications: nerve and skin
Neuropathy
Enquire annually about painful and other symptomatic neuropathy, impotence in men and manifestations of autonomic neuropathy especially if renal complications or erratic blood glucose control. Optimize blood sugar control.
Symmetrical sensory progressive polyneuropathy
Affects 40–50% of patients with DM. Starts distally feet>hands. Glove-and-stocking distribution. May be asymptomatic or cause numbness, tingling, or neuropathic pain. Pain can be depressing and disabling. Be supportive. If simple analgesia with paracetamol or NSAID is ineffective try neuropathic painkillers (Figure 12.2). When pain is controlled, review regularly and consider reducing dose/stopping.
Diabetic neuropathy—steps to pain controlN
Mononeuropathies/mononeuritis multiplex
Especially cranial nerves III and VI— p. 536.
Amyotrophy
Painful wasting of quadriceps muscles—reversible with improved blood sugar control.
Autonomic neuropathy
Postural ↓ BP Common especially in the elderly. Increasing dietary salt intake may help. Other treatments are all unlicensed. They include fludrocortisone 100–400 micrograms od (uncomfortable oedema is a common side effect) ± flurbiprofen or ephedrine hydrochloride (30–60mg tds to relieve oedema), and midodrine (alpha agonist)
Urinary retention p. 454
Diabetic diarrhoea Exclude other causes of change in bowel habit— p. 406. Diabetic diarrhoea can be treated with 2 or 3 doses of tetracycline (250mg—unlicensed). Otherwise treat with codeine phosphate 30mg tds/qds prn
Erectile dysfunction p. 776
Gastric paresis Treat with an antiemetic which promotes gastric transit e.g. domperidone 30mg tds. When this fails, erythromycin may be used but evidence of effectiveness is lacking
Gustatory sweating Can be treated with an antimuscarinic such as propantheline bromide but side effects are common. Hyperhidrosis— p. 603
Depression
Some physical illnesses, including DM, predispose patients to depression. Screen for depression as part of the annual diabetic check ( p. 199)
Skin changes associated with DM
Numerous skin problems are associated with DM. These include:
Predisposition to infection e.g. candidiasis, staphylococcal infection (folliculitis, boils)
Pruritus
Xanthomas
Vitiligo (type 1 DM)
Neuropathic and/or ischaemic ulcers—see the diabetic foot— p. 360
Fat atrophy/hypertrophy at insulin injection sites
Necrobiosis lipoidica—50% associated with DM. Small, dusky red nodules with well-circumscribed borders; can be single or multiple. Usually on the outside of the shin. Enlarge slowly becoming brownish yellow, irregular, and flattened/depressed. Long-standing lesions may ulcerate. No effective treatment
Diabetic dermopathy—pigmented scars over shins
Granuloma annulare 
—asymptomatic dermal nodules; association with DM is controversial
Diabetic cheiroarthropathy—waxy skin thickening over the dorsum of the hand with restricted mobility
For all drugs listed in Figure 12.2, start at low dose and titrate up the dose according to response. Consider lidocaine patches for people with localized pain who are unable to tolerate oral medication.
Further information
NICE www.nice.org.uk
Type 1 diabetes: diagnosis and management (2004)
Neuropathic pain (2010)
The diabetic foot
Foot problems are common amongst people with diabetes—5% develop a foot ulcer in any year (see Table 12.2). Foot problems are due to:
Peripheral neuropathy (affects 20–40% diabetic patients) → ↓ foot sensation, and
Peripheral vascular disease (affects 20–40% diabetic patients) → pain and predisposition to ulceration
| Neuropathic | Vascular |
|---|---|
Warm foot Bounding pulses, normal ABPI Located at pressure points Painless Clearly defined or ‘punched out’ Surrounded by callus | Cool foot Absent pulses, ↓ ABPI Located at extremities (e.g. between toes) Painful Less clearly delineated |
| Neuropathic | Vascular |
|---|---|
Warm foot Bounding pulses, normal ABPI Located at pressure points Painless Clearly defined or ‘punched out’ Surrounded by callus | Cool foot Absent pulses, ↓ ABPI Located at extremities (e.g. between toes) Painful Less clearly delineated |
Information about foot care
Self-care and self-monitoring:
Daily examination of the feet for problems—colour change; swelling; breaks in the skin; numbness
Footwear—importance of well-fitting shoes and hosiery
Hygiene (daily washing and careful drying) and nail care
Dangers associated with procedures, e.g. corn/verruca removal
Methods to help self-monitoring, e.g. mirrors if ↓ mobility
When to seek advice from a health professional—if any colour change, swelling, breaks in the skin, or numbness, or if self-monitoring is not possible (e.g. due to mobility problems)
For patients at increased or high risk or with ulcers, additionally, advise no barefoot walking and that, due to ↓ sensation, extra care and attention is needed
If skin lesions, advise patients to seek help if any change in the lesion, or if ↑ swelling, pain, odour, colour change, or systemic symptoms
Risk factors
Neuropathy
Peripheral vascular disease
Previous ulceration or amputation
Age >70y
Plantar callus
Foot deformities
Poor footwear
Long duration of DM
Social deprivation and isolation
Poor vision
Smoking
The foot check
Check the feet as part of the annual review.
History
Foot problems since last review
Visual or mobility problems affecting self-care of feet
Self-care behaviours and knowledge of foot care
History of numbness, tingling, or burning—may be worse at night
Examination
Foot shape, deformity, joint rigidity, and shoes
Foot skin condition—fragility, cracking, oedema, callus, ulceration, sweating, presence of hair
Foot and ankle pulses
Sensitivity to 10g monofilament or vibration
Management
General points
Optimize diabetic control and risk factors for vascular disease (including smoking cessation)
Review drug therapy—stop β-blockers if peripheral vascular disease
Educate about foot care
Specific management
Classification—Table 12.3
Low risk Foot care education
Increased risk Foot care education. Refer to the foot protection team. Check feet every 3–6mo. Consider referral for vascular assessment. Consider regular podiatry if poor vision, immobility, or poor social conditions/foot hygiene. If previous foot ulcer, deformity, or skin changes manage as high risk
High risk Stress importance of foot care. Refer to the foot protection team for specialist podiatry. Inspect feet every 3–6mo. Review need for vascular assessment. Treat fungal infection
Foot ulcer Refer to the multidisciplinary specialist foot care team urgently. Assess ischaemia using Dopplers. Consider referral for angiography. Treat infection. If new ulceration, cellulitis or discoloration refer to a specialized podiatry/foot care team within 24h
| Foot risk | Features |
|---|---|
Low current risk | Normal sensation, palpable pulses |
Increased risk | Neuropathy, absent pulses, or other risk factors |
High risk | Neuropathy or absent pulses + deformity or skin changes or previous ulcer |
Ulcerated foot | Foot ulcer on examination |
| Foot risk | Features |
|---|---|
Low current risk | Normal sensation, palpable pulses |
Increased risk | Neuropathy, absent pulses, or other risk factors |
High risk | Neuropathy or absent pulses + deformity or skin changes or previous ulcer |
Ulcerated foot | Foot ulcer on examination |
Patients with diabetes may have coexisting peripheral neuropathy and peripheral vascular disease. ABPI may be artificially ↑ due to calcification of vessels.
Charcot osteoarthropathy (Charcot’s joint)
Neuropathic foot damaged because of trauma 2° to loss of pain sensation. If suspected refer immediately to the multidisciplinary foot care team for immobilization and long-term management.
Further information
NICE www.nice.org.uk
Type 1 diabetes: diagnosis and management (2004)
Type 2 diabetes (2008)
Lumps in the thyroid gland and goitres
Faced with a lump in the pre-tracheal region of the neck, ask:
Is it in the thyroid (moves up and down on swallowing)?
Is it a solitary lump or more generalized (a goitre)?
Is the patient thyrotoxic, euthyroid, or hypothyroid?
Is the trachea being compressed (patient is breathless)?
If symptoms of tracheal compression, including stridor due to thyroid swelling.
If thyroid swelling + any of:
Patient aged ≥65y
Solitary nodule increasing in size
History of neck irradiation
FH of an endocrine tumour
Unexplained hoarseness/voice changes
Cervical lymphadenopathy
Very young (pre-pubertal) patient
Request TFTs if thyroid swelling without stridor or any of the features listed above. Do not request USS or isotope scanning
Refer non-urgently to endocrinology Patients with hyper- or hypothyroidism and an associated goitre
Refer non-urgently to a thyroid surgeon Patients with goitre and normal thyroid function tests without any of the features listed above
Solitary thyroid nodules
Investigate all solitary nodules. Check TFTs and refer as above. Differential diagnosis:
Benign (90%): cyst, adenoma, discrete nodule in a nodular goitre
Malignant (10%): primary—thyroid adenocarcinoma, lymphoma, medullary carcinoma; secondary—direct spread from local tumour, metastatic spread from breast, colon/rectum, kidney, lung, lymphoma
Carcinoma of the thyroid
Primary tumours
Papillary adenocarcinoma (60%) Typical age: 10–40y. ♀ > ♂ Low-grade malignancy. Rarely fatal. Spreads to local LNs and/or lung. Sensitive to TSH. Treated with thyroidectomy then life-long thyroxine
Follicular carcinoma (25%) Typical age range: 40–60y. ♀ > ♂. May arise in a pre-existing multinodular goitre. Spreads via bloodstream. Bony secondaries are common. Treatment is with surgery and thyroxine suppression therapy and/or radioactive iodine
Lymphoma (5%) Occurs at any age. May be 1° or 2°. Associated with Hashimoto’s thyroiditis. Staged/treated as for lymphomas elsewhere ( p. 680). Prognosis is good
Anaplastic carcinoma (rare) Typical age: 50–60y. ♀ > ♂. Aggressive tumour. Grows rapidly and infiltrates tissues of the neck. Tracheal compression is common. Metastasizes locally to LNs and via lymphatics. Poor response to treatment
Medullary carcinoma (rare) Occurs at any age. ♀ = ♂. Familial incidence; associated with adenomas elsewhere. Often secretes calcitonin (used as tumour marker). Spreads to local LNs. Treated by excision then chemotherapy ± radiotherapy
Goitre
There are 4 main types of goitre—see Table 12.4.
| Type | Features | Management |
|---|---|---|
Congenital | Enlarged thyroid gland present at birth ± hypo- or hyperthyroidism | Hypothyroid babies are treated with thyroxine; if there is tracheal compression or hyperthyroidism, treatment is surgical |
Physiological | Occurs at puberty, during pregnancy, and in conditions of iodine deficiency | Usually requires no treatment. If iodine deficient, treat with iodine supplements |
Nodular | Benign enlargement of the thyroid gland with areas of hyperplasia and involution | No treatment is necessary unless: • Thyrotoxic • Compression of the neck structures → dyspnoea or dysphagia • Worried by cosmetic appearance • Focal ↑ in size or recurrent laryngeal nerve palsy (hoarseness)—suggests malignant change If treatment is needed, refer to surgery or endocrinology, depending on symptoms |
Toxic | Graves’ disease—smooth thyroid enlargement + thyrotoxicosis | See management of hyperthyroidism— |
Inflammatory | Hashimoto’s thyroiditis: ♀>♂. Antibodies to thyroid tissue are produced. Initially goitre and thyrotoxicosis Later myxoedema | In all cases, refer to endocrinology for confirmation of diagnosis and management guidance |
De Quervain’s thyroiditis: Inflammation due to viral infection—usually Coxsackie virus. Acutely swollen, tender thyroid gland and transient thyrotoxicosis often preceded by sore throat/malaise. Settles spontaneously | ||
Riedel’s thyroiditis: Rare. Infiltrated by scar tissue → hypothyroidism ± recurrent laryngeal nerve palsy ± stridor |
| Type | Features | Management |
|---|---|---|
Congenital | Enlarged thyroid gland present at birth ± hypo- or hyperthyroidism | Hypothyroid babies are treated with thyroxine; if there is tracheal compression or hyperthyroidism, treatment is surgical |
Physiological | Occurs at puberty, during pregnancy, and in conditions of iodine deficiency | Usually requires no treatment. If iodine deficient, treat with iodine supplements |
Nodular | Benign enlargement of the thyroid gland with areas of hyperplasia and involution | No treatment is necessary unless: • Thyrotoxic • Compression of the neck structures → dyspnoea or dysphagia • Worried by cosmetic appearance • Focal ↑ in size or recurrent laryngeal nerve palsy (hoarseness)—suggests malignant change If treatment is needed, refer to surgery or endocrinology, depending on symptoms |
Toxic | Graves’ disease—smooth thyroid enlargement + thyrotoxicosis | See management of hyperthyroidism— |
Inflammatory | Hashimoto’s thyroiditis: ♀>♂. Antibodies to thyroid tissue are produced. Initially goitre and thyrotoxicosis Later myxoedema | In all cases, refer to endocrinology for confirmation of diagnosis and management guidance |
De Quervain’s thyroiditis: Inflammation due to viral infection—usually Coxsackie virus. Acutely swollen, tender thyroid gland and transient thyrotoxicosis often preceded by sore throat/malaise. Settles spontaneously | ||
Riedel’s thyroiditis: Rare. Infiltrated by scar tissue → hypothyroidism ± recurrent laryngeal nerve palsy ± stridor |
Thyroid cyst
Usually degenerative part of a nodular goitre, though true cysts do occur. Rapid enlargement/pain may be caused by haemorrhage into a cyst. Refer for confirmation of diagnosis.
Thyroid adenoma
4 types classified according to histological appearance—papillary, follicular, embryonal, hurtle cell. A few produce thyroxine → thyrotoxicosis. Haemorrhage is rare and results in rapid ↑ in size. Refer for confirmation of diagnosis ± surgery.
Further information
NICE Referral guidelines for suspected cancer (2005) www.nice.org.uk
Thyroid disease
Interpretation of thyroid function tests
See Table 12.5
| Results of TFTs | Interpretation | Notes |
|---|---|---|
TSH ↓, T4↑ | Thyrotoxic | Occasionally T4 is normal but T3↑ |
TSH ↑, T4↓ | Hypothyroid | TSH ↓ if hypothyroidism is secondary to pituitary failure (rare) |
TSH ↑, T4↔ | Subclinical hypothyroidism | If any symptoms (including depression and non-specific symptoms or hypercholesterolaemia) consider a trial of treatment If no symptoms monitor annually |
| Results of TFTs | Interpretation | Notes |
|---|---|---|
TSH ↓, T4↑ | Thyrotoxic | Occasionally T4 is normal but T3↑ |
TSH ↑, T4↓ | Hypothyroid | TSH ↓ if hypothyroidism is secondary to pituitary failure (rare) |
TSH ↑, T4↔ | Subclinical hypothyroidism | If any symptoms (including depression and non-specific symptoms or hypercholesterolaemia) consider a trial of treatment If no symptoms monitor annually |
Hyperthyroidism
Affects 2% ♀ and 0.2% ♂. Peak age: 20–49y. Causes:
Graves’ disease
Toxic nodular goitre—older women with past history of goitre
Thyroiditis
Amiodarone
Kelp ingestion
Presentation
Weight loss
Tremor
Palpitations
Hyperactivity
AF
Hyperhidrosis
Eye changes
Infertility
Alopecia
In elderly patients, symptoms may be less obvious and include confusion, dementia, apathy, and depression.
Management
Refer to endocrinology at presentation. Treatment:
β-blockers (e.g. propranolol, atenolol) Useful for symptom control until antithyroid drug therapy takes effect
Carbimazole Inhibits synthesis of thyroid hormones. Ineffective for treatment of thyroiditis. May be given short-term to render a patient euthyroid prior to surgery or treatment with radioactive iodine, or long-term (12–18mo) in an attempt to induce remission (but >50% relapse). 3/1,000 patients have serious adverse effects—agranulocytosis, hepatitis, aplastic anaemia, or lupus-like syndromes
Radioactive iodine ( 131 I) Effects take 3–4mo to become apparent. Withdraw carbimazole >4d prior to treatment, and do not restart until >3d after. Advise women of childbearing age to avoid pregnancy for 4mo. Most become hypothyroid at some point (sometimes years) after treatment. Continue monitoring TFTs long-term. Associated with small ↑ risk of thyroid malignancy
Surgery Partial or total thyroidectomy—reserved for patients with large goitres or who decline radioactive iodine. Carries risk of damage to recurrent laryngeal nerve or parathyroids
Warn all patients starting carbimazole to stop the drug and seek urgent medical attention if they develop sore throat or other infection.
Thyrotoxic crisis/storm
p. 1101
Graves’ disease
Most common cause of hyperthyroidism. ♀:♂≈ 5:1. Peak age: 30–50y. Associated with smoking and stressful life events. Autoimmune disease in which antibodies to the TSH receptor are produced. R.J. Graves (1797–1853)—Irish physician.
Clinical features
Hyperthyroidism
Diffuse goitre ± thyroid bruit due to ↑ vascularity
Extrathyroid features: thyroid eye disease—25–50% (bilateral in >90%); pretibial myxoedema—5%; thyroid acropachy (clubbing, finger swelling)—rare; onycholysis—rare
Management
As for hyperthyroidism.
Thyroid eye disease
Presents with:
Double vision
Eye discomfort ± protrusion (exophthalmos and proptosis)
Lid lag
Ophthalmoplegia (especially of upward gaze)
TFTs can be ↑ or normal
Management
Refer to ophthalmologist. If ↓ acuity or loss of colour vision—refer urgently as there may be optic nerve compression.
Hypothyroidism (myxoedema)
Common—10% ♀ >60y, ♀:♂≈ 8:1.
Causes
Chronic autoimmune thyroiditis, post-131I, thyroidectomy.
Presentation
Onset tends to be insidious and may go undiagnosed for years. Always consider hypothyroidism when a patient has non-specific symptoms, depression, fatigue, lethargy, or general malaise. Other symptoms—weight ↑, constipation, hoarse voice, or dry skin/hair. Signs are often absent—there may be a goitre, slow-relaxing reflexes, or non-pitting oedema of the hands, feet, or eyelids.
Screening
Check TFTs in patients:
With persistent symptoms of tiredness/lethargy without clear cause
On amiodarone or with a history of 131I administration
With hypercholesterolaemia, infertility, Turner’s or Down’s syndrome, depression, dementia, obesity, DM, or other autoimmune disease
Management
Patients taking thyroxine replacement are entitled to apply for free prescriptions in England ( p. 137).
<65y and healthy 100 micrograms od levothyroxine. Recheck TFTs after 4–6wk. Adjust dose to keep TSH in the normal range. Once dose is stable and TSH is within normal range monitor annually and if symptomatic or worries about compliance. Over-replacement is associated with AF and osteoporosis
If elderly or pre-existing heart disease Start 25 micrograms od levothyroxine and ↑ dose every 4–6wk according to TFTs. Consider adding propranolol if history of CHD as levothyroxine can provoke angina
Withdrawal of levothyroxine
Usually needed life long. If diagnosis is in doubt stop and remeasure TFTs after 4–6wk.
Hypothyroid coma
p. 1101
Information for patients
British Thyroid Foundation 01423 709707 www.btf-thyroid.org
Hyper- and hypocalcaemia
Take an uncuffed sample (to avoid falsely high readings) and correct for serum albumin—for every mmol/L less than 40, a correction of 0.02mmol/L should be added. For example:
Calcium 2.40 | Corrected calcium | = (40 – 24) × 0.02 + 2.4 |
Albumin 24 | = 0.32 + 2.4 = 2.72 |
Calcium 2.40 | Corrected calcium | = (40 – 24) × 0.02 + 2.4 |
Albumin 24 | = 0.32 + 2.4 = 2.72 |
Hypocalcaemia
↓ serum calcium (<2.15mmol/L). Causes:
If phosphate ↑ CRF, hypoparathyroidism (may be congenital or 2° to thyroid or parathyroid surgery, or malignant infiltration), pseudohypoparathyroidism (insensitivity to parathyroid hormone)
If phosphate normal or ↓ Vitamin D deficiency (osteomalacia, rickets), malabsorption, overhydration, pancreatitis
Presentation
May be subtle. Includes:
Tetany
Irritability, depression, or psychosis
Perioral paraesthesia
Carpo-pedal spasm (wrist flexion and fingers drawn together)
Neuromuscular excitability (tapping over parotid causes facial muscles to contract—Chvostek’s sign)
Apparent hypocalcaemia may be an artefact of hypoalbuminaemia.
Management
Check vitamin D levels. Supplement with calcium. Referral may be needed to investigate/treat the underlying cause.
Hypercalcaemia
↑ level of serum calcium (>2.55mmol/L). Prevalence ≈1:500; ♂:♀ ≈1:3. Rare < age 50y.
| Common causes (90%) | Uncommon causes |
|---|---|
• Primary hyperparathyroidism • Malignancy (10% tumours—usually myeloma, breast, lung, kidney, thyroid, prostate, ovary, or colon) | • Chronic renal failure • Familial benign hypercalcaemia • Sarcoidosis • Thyrotoxicosis • Milk alkali syndrome • Vitamin D treatment |
| Common causes (90%) | Uncommon causes |
|---|---|
• Primary hyperparathyroidism • Malignancy (10% tumours—usually myeloma, breast, lung, kidney, thyroid, prostate, ovary, or colon) | • Chronic renal failure • Familial benign hypercalcaemia • Sarcoidosis • Thyrotoxicosis • Milk alkali syndrome • Vitamin D treatment |
Presentation
Often very non-specific. May be an incidental finding. Other symptoms: ‘bones, stones, groans, and abdominal moans’.
Tiredness
Lethargy
Weakness
Mild aches and pains
Anorexia
Weight loss
Low mood
Stone formation
Nausea/vomiting (often intractable)
Polyuria and polydipsia
Abdominal pain
Constipation
Confusion
Corneal calcification
Management
Guide to the diagnosis of cause of hypercalcaemia (must be taken in clinical context)
Hypercalcaemia can be fatal. If Ca2+ >3.5mmol/L or severe symptoms, admit for lowering of Ca2+ with forced diuresis and IV bisphosphonate.
Hyperparathyroidism
↑ secretion of parathyroid hormone (PTH).
1° hyperparathyroidism Incidence 0.5/1,000. Peak age 40–60y. ♀:♂≈ 2:1. Circulating level of PTH is inappropriately high. Most patients are hypercalcaemic (but may be normocalcaemic if coexistent vitamin D deficiency). Due to ↑ secretion of PTH from one or both parathyroid glands. Refer. Treatment is usually surgical
2° hyperparathyroidism ↑ PTH in response to chronic hypocalcaemia or hyperphosphataemia. Treat cause
Tertiary hyperparathyroidism Inappropriately ↑ PTH →↑ Ca2+. Follows prolonged 2° hyperparathyroidism. Most common in patients with chronic renal failure (especially if on dialysis) or chronic malabsorption. Treatment is usually surgical
Familial benign hypercalcaemia
Asymptomatic. Inherited condition in which serum calcium concentrations are mildly ↑ throughout life. Confirm (if possible) by demonstrating ↑ Ca2+ in other family members. No adverse consequences and no treatment needed.
Milk alkali syndrome
Usually due to ingestion of OTC indigestion remedies (e.g. Rennies®). Ca2+ levels revert to normal on stopping. Investigate the reason why the patient is taking these remedies (? peptic ulcer). Sometimes also caused by calcium supplements taken with bisphosphonates for prophylaxis of osteoporosis—stop the calcium supplement.
Adrenal disorders
Disorders of the adrenal cortex
The adrenal cortex produces three classes of steroids:
Glucocorticoids, e.g. cortisol
Mineralocorticoids, e.g. aldosterone, and
Sex hormones, e.g. androstenedione, testosterone, and oestrogen
Symptoms result from disturbance in production of these steroids.
Cushing’s syndrome
In the majority of cases, Cushing’s syndrome is iatrogenic—caused by exogenous administration of prednisolone or other corticosteroids. Non-iatrogenic Cushing’s syndrome is much rarer with annual incidence of 1–2/million (♀:♂ ≈3:1):
80% have a pituitary adenoma which secretes adrenocorticotrophic hormone (ACTH) causing hypersecretion of glucocorticoids and sex hormones (Cushing’s disease)
20% are due to ectopic ACTH secretion by other tumours (e.g. small cell lung cancer) or hypersecreting tumours of the adrenal cortex
H.W. Cushing (1869–1939)—US neurosurgeon.
Presentation
Cushing’s syndrome has high morbidity and mortality. Clinical features include:
Moon face (90%)
Truncal obesity (85%)
Hypertension (80%)
Menstrual disturbance (80%)
Striae and bruising (60%)
Osteoporosis (60%)
Lethargy/depression (60%)
Hirsuitism
Acne
Pigmentation
Feminization in men
Polyuria and polydipsia
Psychosis
Management
Stop/minimize exogenous steroids
If no exogenous steroids and Cushing’s syndrome is suspected, request a dexamethasone suppression test—dexamethasone 1mg po at midnight, then serum cortisol measured at 9 a.m. If <50mmol/L exclude diagnosis unless cortisol secretion is episodic. If ≥50mmol/L check ACTH level and 24h urinary free cortisol and seek expert advice
Adrenal insufficiency (Addison’s disease)
May be:
Primary—resulting from adrenal disease/failure, or
Secondary—resulting from inadequate pituitary or hypothalamic stimulation of the adrenal glands
In the UK, most cases result from autoimmune disease, surgery, cessation of therapeutic corticosteroids, or failure to ↑ steroid dose to cover stress. Worldwide TB and AIDS are major causes. T. Addison (1795–1860)—English physician.
Clinical features
Tiredness (95%)
Weakness (95%)
Anorexia (95%)
Weight loss (90%)
Abdominal pain (30%)
Myalgia/arthralgia (20%)
Postural hypotension/fainting (15%)
Nausea
Pigmentation (buccal, palmar creases, new scars—90%)
Presentation
Can be dramatic with coma and severe hypoglycaemia ( p. 1101—admit as an emergency) or insidious
50% patients with autoimmune Addison’s disease have or will develop another autoimmune disease (e.g. Graves’ disease, pernicious anaemia) and 5% of women develop premature ovarian failure
Short Synacthen® test
Take 9 a.m. blood for serum cortisol levels; inject 250 micrograms Synacthen® IV or IM; take a further blood sample for serum cortisol levels half an hour later. If 30min cortisol level is:
>600nmol/L—adrenal insufficiency is excluded
400–590nmol/L—the result is equivocal; repeat
<400nmol/L—adrenal insufficiency is confirmed; check ACTH (if ↓, investigate pituitary function; if ↑ investigate cause of adrenal disease)
Other investigations
Biochemical abnormalities—↑ K+, ↓ Na+, ↓ glucose (may not be symptomatic), uraemia, ↑ Ca2+, abnormal LFTs
FBC—normocytic anaemia, eosinophilia, lymphocytosis
Management
Refer to endocrinology. Treatment usually involves replacing deficient steroids with hydrocortisone and fludrocortisone.
Warn patients not to stop steroids abruptly, to tell any doctor treating them about their condition and wear Medic-Alert/Medi-Tag bracelet in case of emergency. Double dose of hydrocortisone prior to dental treatment or if intercurrent illness (e.g. URTI). If vomiting, replace hydrocortisone po with IM hydrocortisone.
Hyperaldosteronism
Suggested by presence of ↑ BP resistant to treatment together with ↓ K+—but normokalaemic cases are also described. May be primary (two out of three have an aldosterone-secreting adenoma) when termed Conn’s syndrome, or secondary to excess renin secretion (e.g. due to renal artery stenosis). If suspected, refer for endocrine assessment. Treatment depends on the cause.
Congenital adrenal hyperplasia
p. 894
Disorders of the adrenal medulla
Phaechromocytoma
Rare but serious disorder affecting 0.1% hypertensive patients. Usually caused by catecholamine-secreting tumours—10% are bilateral; 10% are extra-adrenal; 10% occur in children; 10% are malignant. May present with a huge array of symptoms and signs. ↑ BP may be sporadic or sustained. Suspect in patients who:
Are young with ↑ BP
Have very labile BP or sudden onset hypertension
Have ↑ BP and associated headaches, sweating, and/or palpitations
Have other associated conditions (e.g. neurofibromatosis)
Check 24h urine catecholamine/metabolite levels (follow local laboratory protocol). If confirmed or strong suspicion despite −ve test, refer for specialist opinion. Treatment is usually surgical if tumour is found.
Patient advice and support
The Pituitary Foundation 0845 450 0375 www.pituitary.org.uk
Addison’s Disease Self Help Group www.addisons.org.uk
Pituitary problems
Hypopituitarism
↓ production of all pituitary hormones (ACTH, growth hormone, FSH, LH, TSH, and prolactin). Causes:
Surgery
Irradiation
Tumour (may be non-secreting or secrete one pituitary hormone with ↓ secretion of the others)
Infection—TB
Sheehan’s syndrome—pituitary necrosis after post-partum haemorrhage (H.L. Sheehan—English pathologist)
Presentation
Hypothyroidism
Hypogonadism
Anorexia
Headache
Depression
Hair loss
Hypotension
Visual field defect
Management
If suspected refer to neurology or endocrinology for further investigation and advice on treatment.
Pituitary tumours
10% intracranial tumours. Almost all are benign. Classified by histological type (chromophobic, acidophilic, or basophilic) or by the hormone secreted:
No hormone (30%)
Prolactin (35%)
Growth hormone (20%)
ACTH (7%)
Prolactin and growth hormone (7%)
LH, FSH, and TSH (1%)
Presentation
Present with symptoms caused by:
Local pressure—bilateral hemianopia, cranial nerve palsies, headache
Hormone secretion, and/or
Hypopituitarism
Management
If suspected refer for further investigation and treatment.
Pituitary apoplexy
Rapid expansion of a pituitary tumour due to infarction or haemorrhage. Suspect if sudden onset of headache in a patient with a known pituitary tumour. Admit as a medical/neurosurgical emergency.
Craniopharyngioma
Tumour originating from Rathke’s pouch. 50% present with local pressure effects in children. Refer as for pituitary tumours.
Hyperprolactinaemia
The most common pituitary disorder resulting from pituitary adenoma.
Presentation
Tends to present earlier in women than men. Symptoms are due to pressure effects or ↑ prolactin. Symptoms of ↑ prolactin:
♀: loss of libido, weight gain, apathy, vaginal dryness, menstrual disturbance, infertility, galactorrhoea
♂: impotence, ↓ facial hair
Investigation
Check basal plasma prolactin (ask the laboratory for conditions under which they would like the sample taken).
Management
If suspected refer for specialist opinion.
Other causes of ↑ prolactin
Pregnancy
Breastfeeding
Stress
Sleep
Hypothyroidism
Drugs—phenothiazines, metoclopramide, domperidone, SSRIs, methyldopa, oestrogens
Chronic renal failure
Sarcoidosis
Acromegaly
Rare condition due to a growth-hormone-secreting pituitary tumour. Typical age at presentation: 30–50y.
Presentation
Local pressure symptoms
Changes in appearance—coarse oily skin; change in facial appearance with coarsening of features; ↑ foot size; ↑ teeth spacing
Other effects—deepening of voice, sweating, paraesthesia, proximal muscle weakness, progressive heart failure, goitre
Complications—DM, ↑ BP, cardiomyopathy, large bowel tumours
Investigation and management
Refer to endocrinology.
Diabetes insipidus (DI)
Caused by impaired water resorption by the kidney. Two mechanisms:
Cranial DI ↓ ADH secretion from the posterior pituitary. 50% idiopathic. Other causes: head injury, tumour, infection, sarcoidosis, vascular, inherited
Nephrogenic DI Impaired response of the kidney to ADH. Causes: drugs (e.g. lithium), hypercalcaemia, pyelonephritis, hydronephrosis, pregnancy (rare)
Presentation
Polydipsia, polyuria, dilute urine, dehydration.
Investigations
U&E (Na+↑), plasma and urine osmolality (plasma ↑, urine ↓—ratio >1). Specialist investigations (e.g. water deprivation test) confirm diagnosis.
Management
Treat the cause.
Cranial DI may be treated with intranasal desmopressin or surgery
Nephrogenic DI may be treated with dietary restriction of protein and salt and/or bendroflumethiazide
Syndrome of inappropriate ADH (SIADH)
Important cause of hyponatraemia. Diagnosis is made by finding a concentrated urine (sodium >20mmol/L) in the presence of hyponatraemia (<125mmol/L) or low plasma osmolality (<260mmol/kg) in the absence of hypovolaemia, oedema, or diuretics. Always requires specialist management. Causes:
Malignancy, e.g. small cell lung cancer; pancreas; lymphoma
CNS disorders, e.g. stroke; subdural haemorrhage; vasculitis (SLE)
Patient advice and support
The Pituitary Foundation 
0845 450 0375 
www.pituitary.org.uk
Use rapid-acting insulin as an alternative to mealtime soluble insulin where nocturnal or late interprandial hypoglycaemia is a problem or to eliminate the need for snacks between meals.
