++
Doubt about the diagnosis
Severe hyperthyroidism, especially if there is coexisting thyrocardiac disease
Pregnant patients with hyperthyroidism
Progression of exophthalmos
Ideally all cases
++
A thyroid nodule is defined as a discrete lesion on palpation and/or ultrasonography that is distinct from the rest of the thyroid gland.
++
Dominant nodule in a multinodular goitre (most likely)
Colloid cyst
True solitary nodule: adenoma, carcinoma (papillary or follicular)
++
++
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.
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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).
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Hyperprolactinaemia13
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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.
++
Symptoms common to males and females: reduced libido, subfertility, galactorrhoea (mainly females)
Females: Amenorrhoea/oligomenorrhoea
Males: erectile dysfunction, reduced facial hair
++
++
Refer for management, which may include a dopamine agonist such as cabergoline or bromocriptine.
++
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
++
DxT nasal problems + fitting problems (e.g. rings, shoes) + sweating ➜ acromegaly
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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.
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Diabetes insipidus and SIADH
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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.
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DxT weakness + polyuria + polydipsia ➜ diabetes insipidus
++
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
++
DxT (female): amenorrhoea + loss of axillary and pubic hair + breast atrophy ➜ hypopituitarism
DxT (male): ↓ libido + impotence + loss of body hair ➜ hypopituitarism
++
Investigate with serum pituitary hormones, imaging and triple stimulation test.
++
The primary zones of the adrenal gland and their secretions
++
zona glomerulosa—mineral corticoids, especially aldosterone
zona fasciculata—glucocorticoids
zona reticularus—androgens, especially DHEA
++
++
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)
++
Autoimmune destruction of the adrenals is the most common cause.
++
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.
++
DxT fatigue + a/n/v + abdominal pain (± skin discolouration) ➜ Addison disease
++
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.
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Addisonian crisis9,14
++
An Addisonian crisis develops because of an inability to increase cortisol in response to stress, which may include intercurrent infection, surgery or trauma.
++
++
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
++
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.
++
++
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
++
DxT plethoric moon face + thin extremities + muscle weakness ➜ Cushing syndrome
+++
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.
++
Usually asymptomatic and hypertensive but any symptoms are features of hypokalaemia:
++
weakness
cramps
paraesthesia
polyuria and polydipsia
++
++
Refer for treatment including possible surgery to excise adenoma.
+++
Phaeochromocytoma9,12
++
A dangerous tumour of the adrenal medulla. Clinical features are paroxysms or spells of:
++
++
++
+++
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
++
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.
++
Rule: tumours >4 cm require thorough assessment as malignant tumours are large. Excision is usually advisable.
++
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.
++
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.
++
DxT weakness + constipation + polyuria ➜ hypercalcaemia
DxT cramps + confusion + tetany ➜ hypocalcaemia
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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.
++
Exclusion of other causes of hypercalcaemia
Serum parathyroid hormone (elevated)
TC-99m Sestamibi scan to detect tumour
++
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).
++
++
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 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