Chapter 23: Endocrine and metabolic disorders

Endocrine, particularly thyroid, disorders can be a diagnostic trap in family practice and early diagnosis is a real challenge. A family practice of 2500 patients can expect one new case of thyroid disorder each year and 10 ‘cases’ in the practice.¹ The diagnosis of an overactive or underactive thyroid can be difficult as the early clinical deviations from normality can be subtle.

The clinical diagnosis of classical Graves disease is usually obvious with the features of exophthalmos, hyperkinesis and a large goitre but if the eye and neck signs are absent it can be misdiagnosed as an anxiety state. Elderly patients may present with only cardiovascular signs, such as atrial fibrillation and tachycardia, or with unexplained weight loss.

The hypothyroid patient can be very difficult to diagnose in the early stages, especially if the patient is being seen frequently. Hypothyroidism often has a gradual onset with general symptoms such as constipation and lethargy.

If suspected, serum thyroid stimulating hormone (TSH) or thyrotropin should be requested.

Other common endocrine disorders include diabetes mellitus, hyperprolactinaemia, calcium metabolic disorder, PCOS, sexual dysfunction and subclinical hypogonadism. They may be difficult to diagnose in the early stages of development. The pituitary is the master gland and its regulating hormones are depicted in FIGURE 23.1.^2,3

Thyroid function tests

Advances in technology have allowed the biochemical assessment of thyroid function to change dramatically in recent years with the introduction of the serum free thyroxine (T₄) and the monoclonal TSH assays. With the highly sensitive TSH assays it is now possible to distinguish suppressed TSH levels (as in hyperthyroidism) from low and normal levels of TSH. However, the new assays are not foolproof and require interpretation in the context of the clinical picture. The serum TSH level is the most sensitive index of thyroid function and is the preferred test for suspected thyroid dysfunction. If necessary repeat TSH in 3–6 months.

Serum tri-iodothyronine (T₃) measurement and serum free thyroxine (T₄) can be useful in suspected T₃ toxicosis where serum T₄ level may be normal, and for monitoring patients with treated thyroid dysfunction.

The relative values are summarised in TABLE 23.1.

Thyroid auto-antibodies

Raised auto-antibodies (antimicrosomal or antithyroid peroxidase) are suggestive of Hashimoto thyroiditis (autoimmune thyroiditis). Antithyroglobulin, anti-thyroid peroxidase and TSH receptor antibodies are elevated in Graves disease, the TSH receptor antibody being very specific for Graves disease.

Fine needle aspiration

This is the single most cost-effective investigation in the diagnosis of thyroid nodules. It is the best way to assess a nodule for malignancy. Care needs to be taken in the interpretation of the cytology results in conjunction with an experienced cytologist/pathologist.

Thyroid isotope scan

The scan may help in the differential diagnosis of thyroid nodules and in hyperthyroidism. A functioning nodule is said to be less likely to be malignant than a non-functioning nodule (cyst, colloid nodule, haemorrhage are non-functioning; carcinoma is usually non-functioning).

Thyroid ultrasound

A thyroid ultrasound is usually more sensitive in the detection of thyroid nodules. A multinodular goitre may be diagnosed on ultrasound while the clinical impression may be that of a solitary nodule (the other nodules not being palpable clinically). A multinodular goitre is said to be less likely to be malignant than a solitary thyroid nodule. An ultrasound allows for follow-up of thyroid nodule(s) to note if there are any changes in size over a period of time and to then discuss appropriate intervention with the patient. It can also differentiate a solid from a cystic mass.

CT scan

CT scan of the thyroid may be used particularly to determine if there is significant compression in the neck from a large multinodular goitre with retrosternal extension. Again follow-up CT scans may allow one to determine the progression or otherwise of such a goitre.

Hypothyroidism (myxoedema)

Hypothyroidism, which is relatively common, is more prevalent in elderly women (up to 5%).⁴ The term myxoedema refers to the accumulation of mucopolysaccharide in subcutaneous tissues. The early changes are subtle and can be misdiagnosed, especially if only a single symptom is dominant.

Patients at risk include those with:

• previous Graves disease

• autoimmune disorders (e.g. rheumatoid arthritis, type 1 diabetes)

• Down syndrome

• Turner syndrome

• drug treatment: lithium, amiodarone, interferon

• previous thyroid or neck surgery

• previous radioactive iodine treatment of the thyroid

Clinical features

The main features are:

• constipation

• cold intolerance

• tiredness/lethargy/somnolence

• physical slowing

• mental slowing

• depression

• huskiness of voice

• puffiness of face and eyes

• pallor

• loss of hair

• weight gain

Physical examination

See FIGURE 23.2. The main signs are:

• sinus bradycardia

• delayed reflexes (normal muscular contraction, slow relaxation)

• coarse, dry and brittle hair

• thinning of outer third of eyebrows

• dry, cool skin

• skin pallor or yellowing

• obesity

• goitre

Other diverse presentations of thyroid disorders are given in TABLE 23.2.

Hashimoto thyroiditis (autoimmune thyroiditis)

Hashimoto thyroiditis, or lymphocytic thyroiditis, which is an autoimmune thyroiditis, is the commonest cause of bilateral non-thyrotoxic goitre in Australia. Features are:

• bilateral goitre

• classically described as firm and rubbery

• patients may be hypothyroid or euthyroid with a possible early period of thyrotoxicosis

Diagnosis is confirmed by a strongly positive antithyroid microsomal antibody titre and/or fine needle aspiration cytology.³

Hashimoto thyroiditis may present as postpartum hypothyroidism. The hypothyroidism may resolve in 6–12 months or may be permanent.³

Laboratory diagnosis of hypothyroidism

Thyroid function tests (see TABLE 23.1):

• T₄—subnormal

• TSH—elevated (>10 is clear gland failure)

If T₄ is low and TSH is low or normal, consider pituitary dysfunction (secondary hypothyroidism) or sick euthyroid syndrome. A raised TSH and T₄ in normal range denotes ‘subclinical’ hypothyroidism and treatment is appropriate albeit controversial.^2,5

Interpretation of TFTs can be difficult but requires matching to the clinical ‘picture’ and consultant advice.

Other tests

• Serum cholesterol level elevated

• Anaemia: usually normocytic; may be macrocytic

• ECG: sinus bradycardia, low voltage, flat T waves

Management^7,8,9

Confirm the diagnosis, provide appropriate patient education, and refer the patient where appropriate.

Exclude coexisting hypoadrenalism and ischaemic heart disease before T₄ replacement.

Note: Treatment as primary hypothyroidism when hypopituitarism is the cause may precipitate adrenal crisis.

• Thyroxine 50–100 mcg daily, increasing by 25–50 mcg up to 100–200 mcg if required

Note: Start with low doses (25–50 mcg daily) in elderly and those with ischaemic heart disease and 50–100 mcg in others. Avoid overdosage.

• Aim to achieve TSH levels of 0.5–2 mU/L.

• Monitor TSH levels monthly at first. As euthyroidism is achieved, monitoring may be less frequent (e.g. 2–3 months). When stable on optimum dose of T₄, monitor every 2–3 years. Treatment is usually lifelong.

• Ischaemic heart disease. Rapid thyroxine replacement can precipitate myocardial infarction, especially in the elderly.

• Pregnancy and postpartum. Continue thyroxine during pregnancy; watch for hypothyroidism (an increased dose of T₄ is often required).

• Elective surgery. If euthyroid, can stop thyroxine for one week. If subthyroid, defer surgery until euthyroid.

• Myxoedema coma. Urgent hospitalisation under specialist care is required. Intensive treatment is required, which may involve parenteral T₄ or T₃ as liothyronine or thyroxine by slow IV injection.

Neonatal hypothyroidism

Misdiagnosing this serious condition leads to failure to thrive, retarded growth and poor school performance. If untreated it leads to permanent intellectual damage (cretinism). The clinical features of the newborn include coarse features, dry skin, supra-orbital oedema, jaundice, harsh cry, slow feeding and umbilical hernia. It is detected by routine neonatal heel prick blood testing. Thyroxine replacement should be started as soon as possible, at least before 2 weeks of age to avert intellectual retardation.

• Doubt about diagnosis, diagnostic tests or optimum replacement dosage

• Apparent secondary hypothyroidism, severe illness and associated ischaemic heart disease

• Concurrent autoimmune disease

• Hypothyroidism with goitre, postpartum thyroid dysfunction and in the neonate

• Myxoedema coma

Hyperthyroidism (thyrotoxicosis)

Hyperthyroidism is also relatively common and may affect up to 2% of women, who are affected four to five times more often than men (see FIG. 23.3). Graves disease is the most common cause followed closely by nodular thyroid disease.

Causes^3,10

• Graves disease (typical symptoms with a diffuse goitre and eye signs)

• Autonomous functioning nodules/toxic adenoma

• Subacute thyroiditis (de Quervain thyroiditis)—viral origin (suspect if painful thyroid and malaise)

• Excessive intake of thyroid hormones—thyrotoxicosis factitia

• Exogenous iodine excess, e.g. food contamination

• Amiodarone (beware of this drug)

Clinical features

• Heat intolerance

• Sweating of hands

• Muscle weakness

• Weight loss despite normal or increased appetite

• Emotional lability, especially anxiety, irritability

• Palpitations

• Frequent loose bowel motions

Physical examination

See FIGURE 23.4. Signs are (usually):

• agitated, restless patient

• warm and sweaty hands

• fine tremor (place paper on hands)

• goitre

• proximal myopathy

• hyperactive reflexes

• bounding peripheral pulse

• ± atrial fibrillation

• Lid retraction (small area of sclera seen above iris)

• Lid lag

• Exophthalmos

• Ophthalmoplegia in severe cases

Investigations

• T₄ (and T₃) elevated

• TSH level suppressed

• Radioisotope scan

• Antithyroid peroxidase

The isotope scan enables a diagnosis of Graves disease to be made when the scan shows uniform increased uptake. Increased irregular uptake would suggest a toxic multinodular goitre, while there is poor or no uptake with de Quervain thyroiditis and thyrotoxicosis factitia.

Management

• Establish the precise cause before initiating treatment.

• Refer to an endocrinologist to guide treatment.

• Educate patients and emphasise the possibility of development of recurrent hyperthyroidism or hypothyroidism and the need for lifelong monitoring.

• Monitor for cardiovascular complications and osteoporosis.

Treatment^6,8,9

• Radioactive iodine therapy (¹³¹I)

• Thionamide antithyroid drugs (initial doses)

  • – carbimazole 10–45 mg (o) daily starting with 10–20 mg in divided doses depending on disease activity

    or

  • – propylthiouracil 200–600 mg (o) daily in divided doses or methimazole

• Adjunctive drugs

  • – beta blockers (for symptoms in acute florid phase, e.g. propranolol 10–40 mg, 6 to 8 hourly); diltiazem or atenolol are alternatives

  • – lithium carbonate (rarely used when there is intolerance to thionamides)

  • – Lugol’s iodine: mainly used prior to surgery

• Surgery

  • – subtotal thyroidectomy

    or

  • – total thyroidectomy

Treatment (Graves disease)

There is no ideal treatment, and selection of antithyroid drugs, radioiodine or surgery depends on many factors, including age, size of goitre, social and economic factors and complications of treatment.

• Younger patients with small goitres and mild case—18-month course antithyroid drugs

• Older patients with small goitres—as above or radioiodine (preferably when euthyroid)

• Large goitres or moderate-to-severe cases—antithyroid drugs until euthyroid, then surgery or ¹³¹I

• In Australia (as in the US) ¹³¹I is being increasingly used

Treatment (autonomous functioning nodules and toxic adenoma)

Control hyperthyroidism with antithyroid drugs, then surgery or ¹³¹I. Long-term remissions on antithyroid drugs in a toxic nodular goitre are rare.

Treatment (subacute thyroiditis)⁷

Hyperthyroidism is usually transient and follows a surge of thyroxine after a viral-type illness. Symptoms include pain and/or tenderness over the goitre (especially on swallowing) and fever. In the acute phase treatment is based on rest, analgesics (aspirin 600 mg (o) 4–6 hourly) or ibuprofen 200–400 mg (o) and soft foods. Rarely, when pain is severe, corticosteroids may be used. Antithyroid drugs are not indicated but beta-blockers can be used to control symptoms.

Thyroid crisis (thyroid storm)⁹

Clinical features are marked anxiety, weight loss, weakness, proximal muscle weakness, hyperpyrexia, tachycardia (>150 per minute), heart failure and arrhythmias. It is usually precipitated by surgery or an infection in an undiagnosed patient.

It requires urgent intensive hospital management with antithyroid drugs; IV saline infusion, IV corticosteroids, anti-heart failure and antiarrhythmia therapy, especially beta-blockers.

• Doubt about the diagnosis

• Severe hyperthyroidism, especially if there is coexisting thyrocardiac disease

• Pregnant patients with hyperthyroidism

• Progression of exophthalmos

• Ideally all cases

Thyroid nodules

A thyroid nodule is defined as a discrete lesion on palpation and/or ultrasonography that is distinct from the rest of the thyroid gland.

Causes

• Dominant nodule in a multinodular goitre (most likely)

• Colloid cyst

• True solitary nodule: adenoma, carcinoma (papillary or follicular)

Investigations

• Ultrasound imaging

• Fine-needle aspiration cytology

• Thyroid function tests

Thyroid carcinoma⁹

The main presentations are a painless nodule, a hard nodule in an enlarged gland or lymphadenopathy. Papillary carcinoma is the most common malignancy. Although rare compared with non-malignant lesions (such as colloid nodules, cysts, haemorrhage and benign adenomas), it is important not to miss carcinoma because of the very high cure rate with treatment. This often involves total thyroidectomy, ablative¹³¹ I treatment, thyroxine replacement and follow-up with serum thyroglobulin measurements,¹³¹ I/thallium scanning and neck ultrasound. Fine-needle aspiration is the investigation of choice.

PITUITARY DISORDERS

Pituitary tumours¹⁰

These are invariably benign adenomas. They can present with hormone deficiencies, features of hypersecretory syndromes (e.g. prolactin, GH, ACTH) or by local tumour mass symptoms (e.g. headache, visual field loss).

Hyperprolactinaemia¹³

The main causes (of many) are a pituitary adenoma (micro- or macro), pituitary stalk damage, drugs—such as antipsychotics, various antidepressants, metoclopramide, cimetidine, oestrogens, opiates, marijuana—and physiological causes such as pregnancy and breastfeeding.

Clinical features

• Symptoms common to males and females: reduced libido, subfertility, galactorrhoea (mainly females)

• Females: Amenorrhoea/oligomenorrhoea

• Males: erectile dysfunction, reduced facial hair

Diagnosis

• Serum prolactin and macroprolactin assays

• MRI: consider if headache, etc

Refer for management, which may include a dopamine agonist such as cabergoline or bromocriptine.

Acromegaly

Symptoms suggestive of acromegaly include:

• excessive growth of hands (increased glove size)

• excessive growth of tissues (e.g. nose, lips, face)

• excessive growth of feet (increased shoe size)

• increased size of jaw and tongue; kyphosis

• general: weakness, sweating, headaches

• sexual changes, including amenorrhoea and loss of libido

• disruptive snoring (sleep apnoea)

• deepening voice

Diagnosis^9,12

• Plasma growth hormone excess

• Elevated insulin-like growth factor 1 (IGF-1) (somatomedin)—the key test

• X-ray skull and hands

• MRI scanning pituitary

• Consider associated impaired glucose tolerance/diabetes

Obtain old photographs (if possible).

Treatment: pituitary microsurgery.

Diabetes insipidus and SIADH

Impaired secretion of vasopressin (antidiuretic hormone) from the posterior pituitary leads to polyuria, nocturia and compensatory polydipsia resulting in the passage of 3–20 L of dilute urine per day. There are several causes of diabetes insipidus (DI), the commonest being postoperative (hypothalamic-pituitary), which is usually transient only. Other causes of cranial DI include tumours, infections and infiltrations. In nephrogenic DI the kidney tubules are insensitive to vasopressin. Differential diagnosis includes compulsive (psychogenic) water drinking. The syndrome of secretion of inappropriate antidiuretic hormone (SIADH) is caused by cancer (e.g. lung, lymphomas, kidney, pancreas), pulmonary disorders, various intracranial lesions and drugs such as carbamazepine and many antipsychotic agents. Management of SIADH is essentially fluid restriction.

The treatment of DI is desmopressin, usually given twice daily intranasally.

Hypopituitarism⁹

This rare disorder should be considered with:

• a history of postpartum haemorrhage

• symptoms of hypothyroidism

• symptoms of adrenal insufficiency

• symptoms suggestive of a pituitary tumour

• thin, wrinkled skin: ‘monkey face’

• pale ‘alabaster’ skin/hairlessness

Investigate with serum pituitary hormones, imaging and triple stimulation test.

ADRENAL DISORDERS

The primary zones of the adrenal gland and their secretions

Cortex

• zona glomerulosa—mineral corticoids, especially aldosterone

• zona fasciculata—glucocorticoids

• zona reticularus—androgens, especially DHEA

Medulla

• catecholamines—epinepherine, norepinephrine

It is worth keeping in mind these uncommon disorders of the adrenal gland which can be difficult to diagnose in the early stages, namely:

• chronic adrenal insufficiency (Addison disease)—deficiency of cortisol and aldosterone

• Cushing syndrome—cortisol excess

• primary hyperaldosteronism (refer to CHAPTER 86)

Addison disease^9,14

Autoimmune destruction of the adrenals is the most common cause.

Clinical features

• Lethargy/excessive fatigue/weakness

• Anorexia and nausea

• Diarrhoea/abdominal pain

• Weight loss

• Dizziness/funny turns, syncope: hypoglycaemia (rare); postural hypotension (common)

• Hyperpigmentation, especially mucous membranes of mouth and hard palate, skin creases of hands

If Addison disease remains undiagnosed, wasting leading to death may occur. Severe dehydration can be a feature. Delayed diagnosis is a huge problem. Hypertension and heart failure requires careful monitoring.

Diagnosis

• Elevated serum potassium, low serum sodium

• Low plasma cortisol level (fails to respond to synthetic adrenocorticotropic hormone [ACTH])

• The short synacthen stimulation test is the definitive test

• Consider adrenal auto-antibodies and imaging? calcification of adrenals

Treatment: corticosteroid replacement—hydrocortisone/fludrocortisone acetate, other options.

Addisonian crisis^9,14

An Addisonian crisis develops because of an inability to increase cortisol in response to stress, which may include intercurrent infection, surgery or trauma.

• Nausea and vomiting

• Acute abdominal pain

• Severe hypotension progressing to shock

• Weakness, drowsiness progressing to coma

• Establish IV line with IV fluids

• Hydrocortisone sodium succinate 100 mg IV initially and 50–100 mg 4–6 hourly until stable

• Arrange urgent hospital admission

Cushing syndrome⁹

The five main causes are:

• iatrogenic—chronic corticosteroid administration

• pituitary ACTH excess (Cushing disease)

• bilateral adrenal hyperplasia

• adrenal tumour (adenoma, adenocarcinoma)

• ectopic ACTH or (rarely) corticotrophin-releasing hormone (CRH) from nonendocrine tumours (e.g. oat cell carcinoma of lung)

The clinical features (see FIG. 23.5) are caused by the effects of excess cortisol and/or adrenal androgens.

Clinical features

• Proximal muscle wasting and weakness

• Central obesity, buffalo hump on neck

• Cushing facies: plethora, moon face, acne

• Weakness

• Hirsutism

• Abdominal striae

• Thin skin, easy bruising

• Hypertension

• Hyperglycaemia (30%)

• Menstrual changes (e.g. amenorrhoea)

• Osteoporosis

• Psychiatric changes, especially depression

• Backache

Diagnosis (apart from iatrogenic cause)

• Cortisol excess (plasma or 24-hour urinary cortisol)

• Dexamethasone suppression test

• Inferior petrosal sinus sampling

• Serum ACTH

• Radiological localisation: MRI for ACTH-producing pituitary tumours; CT scanning for adrenal tumours

Primary hyperaldosteronism⁹

Most commonly due to an adrenal adenoma.

Conn syndrome

Usually asymptomatic and hypertensive but any symptoms are features of hypokalaemia:

• weakness

• cramps

• paraesthesia

• polyuria and polydipsia

Investigations

• aldosterone (serum and urine) ↑

• plasma renin ↓

• Na ↑, K ↓, alkalosis

• imaging (MRI or CT scan) of adrenals

Refer for treatment including possible surgery to excise adenoma.

Phaeochromocytoma^9,12

A dangerous tumour of the adrenal medulla. Clinical features are paroxysms or spells of:

• hypertension

• headache (throbbing)

• sweating

• palpitations

• pallor/skin blanching

• rising sensation of tightness in upper chest and throat (angina can occur)

Investigations

• Series of three 24-hour free catecholamines ↑ VMA

• Abdominal CT or MRI scan

Treatment

• Excise tumour, cover with alpha and beta blockers

Congenital adrenal hyperplasia (adrenogenital syndrome)^7,9

An AR condition with 21-hydroxylase deficiency being the most common of several forms. There is inadequate synthesis of cortisol and aldosterone with increased androgenisation. Major problem is adrenal failure ± salt-losing state (SLS). In females, ambiguity of external genitalia and hirsutism before puberty usually occurs. Males may have normal urogenital development but SLS is a concern. Infants of either sex may present with failure to thrive or vomiting and dehydration (SLS). Lifelong glucocorticoid treatment is required. Wearing an alert bracelet or necklace is strongly recommended for these patients (www.medicalert.org.au).⁷

Adrenal tumours¹⁰

Most of those detected by abdominal imaging are benign and termed ‘incidentalomas’ but serious tumours include adrenal carcinoma, phaeochromocytoma, neuroblastoma, glucocorticoid or a mineral corticoid secreting tumour.

Incidentalomas

An important issue is malignancy, and if this is the case, whether it is primary, secondary or functional (hormone secreting).

Investigations to consider include electrolytes, aldosterone/rennin ratio, catecholamines, testosterone, DHEAs, dexamethasone suppression test, CT scan. Surgical excision should be considered under specialist guidance.

CALCIUM DISORDERS

Hypercalcaemia^12,15

Suspect hypercalcaemia if there is weakness, tiredness, malaise, anorexia, nausea or vomiting, abdominal pain, loin pain, constipation, thirst, fever, polyuria, drowsiness, dizziness, personality changes, muscle aches and pains, visual disturbances. Measure urea and electrolytes (especially calcium), creatinine, albumin.

Primary hyperparathyroidism, familial hypercalciuric hypercalcaemia and neoplasia, especially lung and breast (with metastases to bone), account for over 90% of cases. Other causes include Paget disease, Williams syndrome, prolonged immobilisation, sarcoidosis and milk-alkali syndrome. Investigations include ESR, serum parathyroid hormone (N: 1.0–7 pmol/L), serum ACE levels, serum alkaline phosphatase, chest X-ray, Sestamibi scan and bone scan. Requires specialist referral.

Primary hyperparathyroidism¹²

Hyperparathyroidism is caused by an excessive secretion of parathyroid hormone and is usually due to a parathyroid adenoma. The classic clinical features of hyperparathyroidism are due to the effects of hypercalcaemia. Rarely, a parathyroid crisis in a misdiagnosed patient may result in death from severe hypercalcaemia.

Classic mnemonic: bones, moans, stones, abdominal groans.

Diagnosis

• Exclusion of other causes of hypercalcaemia

• Serum parathyroid hormone (elevated)

• TC-99m Sestamibi scan to detect tumour

Hypocalcaemia^9,15

Causes include parathyroid injury, autoimmune hyperparathyroidism, severe vitamin D deficiency and neonates of mothers with hypercalcaemia. This usually presents with tetany or more generalised neuromuscular hyperexcitability and neuropsychiatric manifestations. The sensory equivalents are paraesthesia in the hands, feet and around the mouth (distinguish from tetany seen in the respiratory alkalosis of hyperventilation). There may be seizures and cramps. The diagnosis is by measurement of serum total calcium concentration in relation to serum albumin (s. calcium <2.10 mmol/L).

Two important signs are:

• Trousseau sign: occlusion of the brachial artery with BP cuff precipitates carpopedal spasm (wrist flexion and fingers drawn together)

• Chvostek sign: tapping over parotid (facial nerve) causes twitching in facial muscles

Treatment involves careful adjustments in dosage of calcitriol and calcium to correct hypocalcaemia and avoid hypercalcaemia and hypercalciuria (the latter may lead to kidney impairment).

Hypoparathyroidism

Hypoparathyroidism is the most common cause of hypocalcaemia. Causes include postoperative thyroidectomy and parathyroidectomy, congenital deficiency (DiGeorge syndrome) and idiopathic (autoimmune) hypoparathyroidism. The main features are neuromuscular hyperexcitability, tetany and neuropsychiatric manifestations.

Other electrolyte disturbances

Hypernatraemia Na⁺ >145 mmol/L

• water depletion (e.g. diabetes insipidus)

• water and sodium depletion (e.g. diarrhoea)

• corticosteroid excess (e.g. Cushing syndrome, Conn syndrome)

• iatrogenic: excess IV hypertonic Na solutions

• thirst, confusion, lethargy, weakness, irritability, oliguria

• orthostatic hypotension

• muscle twitching or cramps

• signs of dehydration

• severe: seizures, delirium, hyperthermia, coma

Hyponatraemia Na⁺ <135 mmol/L

• water retention (e.g. CCF, hypoalbuminaemia)

• kidney failure to conserve salt (e.g. nephritis, diabetes mellitus, Addison disease)

• gastrointestinal loss of Na⁺ (e.g. vomiting, diarrhoea)

• drugs (e.g. diuretic excess, ACE inhibitors)

• anorexia, nausea, lethargy, confusion, headache, mental changes (e.g. in personality)

• severe: convulsions, coma, death

Hyperkalaemia K⁺ >5.5 mmol/L

The first sign of hyperkalaemia (e.g. >6) may be a cardiac arrest. A medical emergency if >6.5.

• oliguria, kidney failure

• acidosis (especially metabolic)

• mineralocorticoid deficiency: Addison disease, aldosterone antagonists

• excessive intake of K⁺ (e.g. IV fluids with K)

• drugs (e.g. spironolactone, ACE inhibitors, NSAIDs, suxamethonium)

• Consider artefact, e.g. haemolysed sample

• malaise, muscle weakness, flaccid paralysis (rare)

• may be asymptomatic until cardiac toxicity

• may cause cardiac arrest—asystole or fibrillation

• ECG: peaked T waves, ↓ QT, ↑ PR interval → arrhythmias

Hypokalaemia K⁺ <3.5 mmol/L

If <2.5 severe symptoms, seek urgent attention.

• kidney disease

• gastrointestinal loss: vomiting, diarrhoea

• alkalosis

• mineralocorticoid excess

• loss of extracellular fluid to intracellular (e.g. burns, other trauma, pyloric stenosis)

• drugs (e.g. diuretics: frusemide, thiazides), purgatives, liquorice abuse

• reduced intake of K⁺

• lethargy, muscle weakness and cramps, mental lethargy and confusion

• severe flaccid paralysis, tetany, coma

• ECG: prominent U waves, depressed ST segment, T waves, arrhythmias

Hand-out sheets from Murtagh’s Patient Education 7th edition:

• Hyperthyroidism

• Hypothyroidism

• Goitre (thyroid swelling)