Key Points
Patients with endocrine disease are a heterogeneous group and may present for surgery for their underlying condition (hypo- or hyper-secretion), for related co-morbidities or for unrelated illness.
Endocrine disease can affect all organ systems, so comprehensive preoperative assessment is essential.
In addition to hormonal and metabolic issues, endocrine disease can cause technical problems with airway management or even IV access.
Endocrine disease can also affect fluid balance, drug metabolism and excretion.
Meticulous history taking, physical examination, requests for specific tests and preoperative optimisation of drug therapy are essential for the safe management of a diverse and challenging group of patients.
For anaesthetists, preoperative assessment focusses on the cardiovascular and respiratory systems and other conditions tend to fall into the group of ‘miscellaneous disorders’. However, patients with endocrine disease present many unique challenges for preoperative assessment and management, as their condition not only affects metabolic and hormonal issues, but also has a direct impact on all major organ systems, affects drug handling and excretion and can pose technical problems such as difficulty in intubation. Hence, meticulous history taking, physical examination, requests for specific tests and preoperative optimisation of drug therapy are essential for the safe management of a diverse but fascinating group of patients.
An overview of the human endocrine system is beyond the scope of this chapter, but in brief, the hypothalamic-pituitary axis is the major neuroendocrine organ of the body (Nicholson and Hall, 2014). Regulation of hormone secretion is undertaken by feedback loops, both positive and negative. A typical pathway involves secretion of a releasing factor from the hypothalamus, such as a corticotrophin-releasing factor or hormone (CRF or CRH), which stimulates the anterior pituitary to secrete adrenocorticotrophic hormone (ACTH) into the circulation. In turn, this acts on the target organ, the adrenal cortex, to secrete cortisol. An increase in the circulating concentration of cortisol acts on the hypothalamus and pituitary to inhibit release of CRF and ACTH, respectively, so restoring circulating cortisol levels to normal physiological values. With the exception of prolactin, which is under inhibitory control, mediated by dopamine, the hypothalamic output is largely stimulatory. However, the hypothalamic-pituitary output is also affected by inputs from higher brain centres, including temperature, exercise, stress, altered sleep patterns and steroid hormone concentrations.
The hypothalamus is part of the anterior diencephalon, the most rostral part of the brainstem, and contributes to the floor and lateral wall of the third ventricle. There are vascular connections between the hypothalamus and the anterior lobe of the pituitary, the portal hypophysial vessels, whereas the posterior pituitary is linked to the hypothalamus by neural connections, the hypothalamo-hypophysial tract, arising from cell bodies in the supraoptic and paraventricular nuclei. The pituitary gland is located at the base of the brain and lies within the sella turcica, a bony fossa at the base of the skull. The key difference between the anterior and posterior pituitary results from their embryological origins. The anterior pituitary is derived from Rathke’s pouch, an evagination from the roof of the pharynx, while the posterior lobe arises from an evagination of the third ventricle. Other than neuroendocrine control, the hypothalamus has important functions in temperature regulation, appetite control and sexual behaviour.
The anterior pituitary secretes six hormones in response to releasing factors secreted into the hypophysial vessels in the hypothalamus:
adrenocorticotropic hormone (ACTH)
growth hormone (GH)
prolactin (PRL)
thyroid-stimulating hormone (TSH)
luteinising-stimulating hormone (LSH)
follicle-stimulating hormone (FSH).
The posterior pituitary secretes arginine vasopressin (AVP) and oxytocin.
Hyper- or hypo-secretion of pituitary hormones or end-organ hormones results in a variety of clinical conditions, and patients with endocrine disease may require surgery to address the underlying pathology or the effects on other systems.
The Patient with Pituitary Disease
The most common lesions of the hypothalamic-pituitary axis are benign adenomas of the anterior lobe of the pituitary gland. Only a certain proportion of these adenomas are clinically manifest and pituitary lesions are found in up to 25 per cent of post mortems. Pituitary adenomas present due to the symptoms of hypersecretion, because of pressure or mass effects or a combination of both. Prolactinomas are the most common functional pituitary adenoma, but do not present pathophysiological problems for anaesthetic management. Tumours secreting ACTH or TSH have significant physiological effects and will be discussed under adrenal and thyroid disease headings (vide infra). Tumours causing overproduction of GH present with features of both hypersecretion and pressure effects. Moreover, since the pathophysiological effects present very gradually over years, there is often a considerable interval between the onset of symptoms and diagnosis.
Growth hormone, a 191 amino acid, has mixed catabolic and anabolic effects in the body. Its effects are achieved via the stimulation of the production of polypeptides in the liver which are known as somatomedins or insulin-like growth factors (IGFs). The main protein is called somatomedin C (or IGF 1) which reduces protein catabolism and specifically promotes bone and muscle growth. Glycogenolysis and lipolysis are also promoted by GH, while glucose uptake and use by cells is inhibited, sparing glucose for neurone usage. Symptoms due to an excess of growth hormone are due to direct hormonal effects as well as enlargement of organs with associated problems. Acromegaly is the clinical syndrome resulting from GH excess (Katznelson et al., 2011). Classically, the head, jaw, tongue, lips, hands and feet are considerably enlarged. Facial features are coarsened and the voice is husky. Other features of the disease include profuse sweating and seborrhoea, kyphoscoliosis, muscle weakness and arthralgia and osteoarthritis. Hypertension and left ventricular hypertrophy are present in 40–50 per cemt of acromegalic patients and may be difficult to treat. Symptoms resulting from a mass lesion include headaches, and visual disturbances – classically a bi-temporal hemianopia due to compression of the optic chiasm (Table 17.1).
Table 17.1 Clinical features of acromegaly and anaesthetic implications.
The patient with acromegaly presents perioperative airway difficulties, for a number of reasons. Firstly, bag-mask ventilation may be hard to achieve due to the large jaw and macroglossia; laryngoscopy and intubation may be difficult due to the aforementioned macrognathia and macroglossia, as well as enlargement of the soft tissues of the pharynx, larynx and tracheal mucosa. There may also be glottic stenosis, fixation of the vocal cords or chondrocalcinosis of the larynx. Soft tissue enlargement may also make insertion of devices such as an intubating laryngeal mask more problematic. Although most studies have shown that acromegalic patients can be successfully intubated using standard techniques, awake fibre-optic intubation should be considered and discussed preoperatively if problems are anticipated. Post-operatively, the acromegalic patient may be at risk of airway obstruction or sleep apnoea and should be cared for in a high-dependency unit or ITU.
Preoperative assessment, therefore, includes a meticulous cardiorespiratory assessment and airway evaluation, remembering that many of the complications of GH excess will persist after surgery. Sleep apnoea can affect up to 70 per cent of patients and is associated with an increased risk of post-operative cardiorespiratory problems. Patients should be specifically questioned about snoring, disturbed sleep, daytime somnolence and poor concentration during the day. For further details please see Chapter 6, page 81. Polycythaemia implies significant sleep apnoea with accompanying right heart failure and fluid retention. In addition to routine FBC, urea and electrolytes, chest X-ray and ECG, patient should have an echocardiogram to assess cardiac performance and provide an estimate of pulmonary artery pressures. Concurrent diabetes mellitus should be excluded. A role for medical therapy for somatostatin analogues before surgery has been suggested.
Diabetes Insipidus (DI)
Central diabetes insipidus is due to failure of the posterior lobe of the pituitary with resulting loss of secretion of ADH (antidiuretic hormone or vasopressin). The function of ADH is to conserve water and sodium chloride and it also has vasoconstrictor effects, hence vasopressin. Its secretion is controlled mainly by changes in plasma osmolality (an increase in plasma osmolality stimulates ADH secretion), which are detected by hypothalamic osmoreceptors and changes in blood volume and blood pressure detected by baroreceptors in the heart, aortic arch and carotid sinus. DI may be due to posterior pituitary failure or secondary to a wide variety of other neurological conditions, including head injury or tumour. The clinical signs and symptoms include polyuria and polydipsia with production of large amounts of dilute urine, hypovolaemia and hypernatraemia with an increased plasma omolality (from the normal range of 275–295mosm. kg−1). Preoperative assessment and management focusses on the underlying cause of DI as well as treatment with desmopressin (1-deamino-8-D-arginine vasopressin, DDAVP), the synthetic analogue of AVP, which has a longer half-life but is devoid of vasoconstrictor properties.
The Patient with Diabetes Mellitus
Diabetes mellitus (DM) is the most common endocrine disease and consists of a group of related disorders in which the defining characteristic is hyperglycaemia due to an absolute or relative lack of insulin from the beta cells of the Islets of Langerhans in the pancreas. The majority of patients with DM fall into two groups, those with type 1 or type 2 DM. In the United Kingdom, at least 4–5 per cent of the population has diabetes, and the prevalence is estimated to increase by more than 50 per cent over the next decade as a consequence of obesity, lack of exercise, increased migration of susceptible patients and an ageing population. Type 1 (insulin-dependent DM, juvenile-onset DM) is considered to be due to autoimmune destruction of the β cells of the pancreas and results in an absolute deficiency of insulin. Type 2 diabetes (non-insulin-dependent DM, maturity onset DM) accounts for approximately 90 per cent of all cases of DM and is believed to be caused by obesity and lifestyle, particularly in genetically susceptible individuals. A positive family history increases the risk of developing type 2 DM by almost 2.5 fold. Since the prevalence of diabetes mellitus is increasing, it is inevitable that the number of diabetic patients presenting for surgery also increases. Surgery may be undertaken for the complications of DM, such as coronary artery disease, peripheral vascular disease and renal failure, or the diabetes may be unrelated to the surgical procedure. Diabetes leads to increased morbidity and increased length of hospital stay, thereby increasing inpatient costs (www.diabetes.org.uk. Management of adults with diabetes undergoing surgery and elective procedures: improving standards. September 2015).
Scrupulous preoperative assessment and decisions about fluid management, optimal blood glucose concentrations and knowledge of the newer drugs available can all improve patient outcome (Nicholson and Hall, 2011a). It is first important to establish which type of DM (type 1 or 2) the patient has, the duration of his or her illness and current treatment; this will provide information on whether the disease is long-standing and whether the patient is likely to have some of the micro- and macrovascular complications. A recent HbA1C (glycosylated haemoglobin) value will provide additional information on the adequacy of glycaemic control over the preceding 3 months.
Cardiovascular disease is common in diabetic patients and is often clinically silent. The risk of developing cardiovascular disease is three times higher in diabetic compared with non-diabetic patients, and ischaemic heart disease (IHD) is the main cause of morbidity and mortality. Diabetic patients are at increased risk of coronary artery disease, peripheral vascular disease, hypertension and cerebrovascular disease. A concurrent autonomic neuropathy will increase the risk of perioperative hypotension and arrhythmias. If diabetes is long-standing, it is wise to proceed as if the patient is at risk, despite a lack of reported symptoms. Approximately 70 per cent of patients with diabetes undergoing surgery have one or more cardiovascular complications. In addition, 25 per cent have microvascular disease, of whom 15 per cent have nephropathy. Patients with impaired cardiovascular function and/or nephropathy are also at greater risk of fluid overload.
Renal disease is also common and occurs in 30–40 per cent of patients. Nephropathy will adversely affect drug handing and excretion of many drugs. The onset of clinical nephropathy is preceded by a period of increased urinary microalbuminuria. Because the microvascular complications of DM affect the target organs simultaneously, if a patient has a retinopathy, they usually have a nephropathy as well.
Neuropathies affect up to 50 per cent of patients and can be peripheral neuropathies, mononeuropathies and autonomic neuropathies. The full extent of a peripheral neuropathy should be documented in any patient in whom regional anaesthesia is being considered. Although there is no evidence that central neuraxial blockade will worsen a peripheral neuropathy, there is some evidence that peripheral nerves are more susceptible to trauma or local anaesthetic toxicity. Many patients with a diabetic autonomic neuropathy (DAN) do not have symptoms, but complaints of diarrhoea or constipation, excessive sweating, postural hypotension or impotence are highly suggestive of DAN. Although anaesthetists do not routinely test for DAN, loss of heart rate variability in response to a Valsalva manoeuvre and the presence of orthostatic hypotension will confirm the presence of some degree of DAN. This in turn will increase the risk of intraoperative haemodynamic instability, including bradycardia and hypotension, and is a major risk factor for ventricular arrhythmias and sudden death in patients with long-standing DM, particularly in those undergoing cardiac or vascular surgery. Gastroparesis will result in an increased volume of gastric contents and risk of aspiration.
Airway management can be problematic in type 1 DM patients. The stiff joint syndrome is thought to be due to the pathological glycosylation of tissues resulting from hyperglycaemia, and can affect cervical and laryngeal joints, making laryngoscopy and intubation more difficult. This combined with gastroparesis will worsen the risk of regurgitation and aspiration. Stiff joint syndrome can be diagnosed at the bedside by asking the patient to ‘pray’ or oppose the palmar surfaces of their palms together. Stiffness of the interphalangeal joints results in failure of opposition of fingers and palms, a positive prayer sign.
Preoperative investigations of the diabetic patient are listed in Tables 17.2 and 17.3.
Table 17.3 Additional testing in diabetic patients.
| Transthoracic echocardiography |
| Exercise stress testing |
| Diabetic autonomic neuropathy (DAN), loss of heart rate variability |
| Lung function tests |
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