Thirst and polyuria

Excessive thirst (polydipsia) and increased urine output (polyuria) are the most important presenting symptoms of diabetes mellitus; these are discussed in detail in Chapter 17. Polydipsia and polyuria may also be due to impairment of renal concentrating capacity as a result of a deficiency of antidiuretic hormone (cranial diabetes insipidus) or a failure of antidiuretic hormone action (nephrogenic diabetes insipidus). The latter may be inherited or may occur secondary to impairment of antidiuretic hormone action by hypercalcaemia or hypokalaemia. Sometimes, apparent polydipsia and polyuria may be due to increased fluid intake, which at its most extreme may be vastly excessive (psychogenic polydipsia). The distinction between psychogenic polydipsia and diabetes insipidus is important. Generally, nocturnal polyuria is not a feature of psychogenic polydipsia, but this is not an absolute distinction and further investigation of urine concentrating capacity is usually required.

Weight loss

Loss of weight is a feature of decreased food intake or increased metabolic rate. Sometimes both factors may operate to reduce body weight, as in the cachexia of malignant disease. Thyroid overactivity (hyperthyroidism) is nearly always associated with a combination of weight loss and increased appetite, although occasionally the latter may be stimulated more than the former so that there is a paradoxical increase in weight. Weight loss is rarely the sole presenting symptom of hyperthyroidism and other clinical features often predominate, particularly in younger patients (Box 16.1). In the elderly, however, hyperthyroidism may be occult or may simulate the gradual weight loss of malignant disease. Cardiac arrhythmias are a frequent feature in the elderly. Anorexia nervosa, a psychogenic disorder characterized by a long history of low body weight in the absence of other features of ill health, must be considered, especially in young women. Any form of weight loss may be associated with amenorrhoea.

Other endocrine conditions in which weight loss is a major feature are listed in Box 16.2. Weight loss associated with diabetes mellitus is discussed in Chapter 17.

Weight gain or redistribution

An increase in body weight (Box 16.3) is a predictable result of a reduction in metabolic rate. Weight gain is therefore a common feature of primary hypothyroidism. However, obesity is rarely a consequence of specific endocrine dysfunction, an exception being the recently described but very rare phenomenon of leptin deficiency. In the majority of patients, ‘simple obesity’ is due to a longstanding imbalance between energy intake and expenditure; it frequently begins in childhood and is often present in more than one family member. Glucocorticoid hormone excess (Cushing’s syndrome) results in an increase in body fat predominantly involving abdominal, omental and interscapular fat (truncal obesity), with paradoxical thinning of the limbs due to muscle atrophy.

Muscle weakness

Symptomatic muscular weakness not due to neurological disease is a feature of several metabolic disorders, including thyrotoxicosis, Cushing’s syndrome and vitamin D deficiency. In all these conditions, the metabolic myopathy (Box 16.4) causes symmetrical proximal weakness, mainly involving the shoulder and hip girdle musculature. There is usually associated muscle wasting. The major symptom is difficulty in climbing stairs, boarding a bus or rising from a sitting position. Most patients with hyperthyroidism have proximal weakness. This may be subclinical; it is best demonstrated by asking the patient to rise from the squatting position. The proximal myopathy of vitamin D deficiency is often painful, in contrast to other causes. The differential diagnosis of painful proximal muscular weakness includes polymyositis and polymyalgia rheumatica, as well as spinal root or plexus disease.

Cold intolerance

An abnormal sensation of cold, out of proportion to that experienced by other individuals, may indicate underlying hypothyroidism (Boxes 16.5 and 16.6). This symptom differs from the localized vasomotor symptoms in the hands found in Raynaud’s phenomenon and is rather non-specific, especially in the elderly.

Heat intolerance

The increased metabolic rate of thyrotoxicosis may be associated with heat intolerance in which, at its most extreme, the patient is comfortable at an ambient temperature that others find unpleasantly cold. This is an important symptom, highly specific for thyroid overactivity, which may partly explain some of the seasonal variation in presentation of the condition.

Increased sweating

Hyperhidrosis (excessive sweating) may be a constitutional abnormality, characterized by onset in childhood or adolescence and, sometimes, by a family history. A recent increase in sweat secretion, on the other hand, may be an early indication of thyroid overactivity. Paroxysmal sweating is a common feature of anxiety. Increased catecholamine secretion from a phaeochromocytoma of the adrenal medulla is a rare cause of hyperhidrosis. Intermittent sweating after meals (gustatory hyperhidrosis) may occur in patients with autonomic dysfunction. Growth hormone excess (acromegaly) also increases sweating, perhaps because of hypertrophy of the sweat glands, and this feature can be used to assess the activity of the disease in the clinic. Increased sweating should be distinguished from flushing that occurs physiologically at the time of the natural menopause. Flushing may be a presenting feature of serotonin-secreting carcinoid tumours of the gut and usually indicates extensive disease with hepatic metastases.

Tremor

A fine rapid resting tremor is one of the cardinal clinical features of thyrotoxicosis. This must be distinguished from the coarser and more irregular tremor of anxiety, which is usually associated with a cool peripheral skin temperature, in contrast to the warm skin of the thyrotoxic patient. Tremor due to neurological disease is greater in amplitude, slower in rate, and may be present at rest, as in Parkinson’s disease, or on movement, as in cerebellar tremor. It therefore rarely simulates thyrotoxic tremor. Essential tremor is not so rapid as thyrotoxic tremor, is variable and is worse in certain postures. It often involves the head and neck.

Palpitations

Palpitations are a heightened, unpleasant awareness of the heart beat. They may be a feature of thyrotoxicosis, but are more likely to be due to anxiety. Awareness of the heartbeat while lying down is normal. Other causes of rapid heart rate include paroxysmal tachyarrhythmias. The sensation of intermittent forceful cardiac contraction, sometimes described by the patient as a missed beat, is often due to a compensatory pause following an ectopic beat, and is usually a normal phenomenon.

Postural unsteadiness

Dizziness, or a sensation of faintness on standing, should prompt measurement of lying and standing blood pressure. Postural hypotension, a fall of diastolic blood pressure on standing, occurs with reduced blood volume. In the absence of obvious bleeding or gastrointestinal fluid loss, adrenal insufficiency should be considered. Postural hypotension is frequently due to autonomic neuropathy, especially in longstanding diabetes mellitus. It is also a common complication of any drug therapy for essential hypertension. The drug history is particularly important in the elderly patient with dizziness.

Visual disturbance

Several endocrine conditions may cause visual symptoms. Decreased visual acuity may be due to space-occupying lesions compressing the optic nerve. For example, severe dysthyroid eye disease and orbital or retro-orbital tumours may present in this way. Bitemporal hemianopia (bilateral loss of part or all of the temporal fields of vision), often asymmetrical or incongruous, is a major feature of suprasellar extension of pituitary adenomas compressing the optic chiasm, but may occur in other tumours in this location. Double vision (diplopia) on lateral or upward gaze often results from medial or lateral rectus muscle tethering in dysthyroid eye disease. Apparent magnification of vision (macropsia) can occur in hypoglycaemia.

Fasting symptoms

Tachycardia, sweating and tremor occurring intermittently, especially when fasting, are suggestive of hypoglycaemia. These symptoms resemble those associated with the increased sympathetic drive found in states of fear or with excess secretion of noradrenaline (norepinephrine), as in phaeochromocytoma. In severe persistent hypoglycaemia, these symptoms may progress to decreased consciousness. This is a serious emergency implying neuroglycopenia sufficient to impair brain function. Spontaneous or fasting hypoglycaemia can be due to the following:

Cramps and ‘pins and needles’

Intermittent cramp and ‘pins and needles’ (paraesthesiae), especially if bilateral, can be due to a decreased level of circulating ionized calcium. This may occur in hypoparathyroidism or be associated with a fall in the ionized component of serum calcium, owing to an increased extracellular pH (alkalosis). The latter may occur with any alkalosis, but is particularly well recognized in hyperventilatory states (respiratory alkalosis) and hypokalaemia (metabolic alkalosis). Refractory cramping symptoms after correction of hypocalcaemia can be due to an associated hypomagnesaemia. However, the differential diagnosis of paraesthesiae in the hands includes median nerve compression at the wrist (carpal tunnel syndrome), a syndrome that is usually accompanied by typical sensory and motor disturbance suggestive of a lesion in the median nerve (see Ch. 14).

Nausea

This is a rare symptom of endocrine disease. It is an important presenting feature of adrenal insufficiency, in which typically it is maximal in the morning and may be associated with vomiting. Similar symptoms may occur with severe hypercalcaemia and may be the sole manifestation of this condition. These two conditions should be considered early in the differential diagnosis of a patient presenting with upper gastrointestinal symptoms in the absence of demonstrable structural disease. Occasionally, thyrotoxicosis may present with nausea and vomiting, although looseness of stools is the more common gastrointestinal manifestation of this condition.