A 52-year-old female patient presented with general weakness, headaches and occasional dizziness for the past three months. She had also had occasional abdominal discomfort, moderate anorexia, and minimal intermittent weight loss due to nausea. She tired more easily than before and had a degree of anhedonia.
She was normally well, had a balanced diet and was not on regular medication. Her periods had stopped three years ago and menopausal symptoms had lessened since.
She seemed frustrated and concerned, and had done some research into possible causes for her symptoms. She was unaware of any possible reason for anaemia and there was no family history of thyroid problems, but she indicated she would like these two possibilities ruled out.
The patient's examination seemed unremarkable, with a sitting BP of 124/74 mmHg, a regular pulse rate of 66, a BMI of 22 kg/m2, no apparent goitre, normal looking skin, and a normal abdominal examination.
There was no focal weakness in her limbs and the Romberg test was negative. An ear, nose, and throat examination and a brief check of the cranial nerves were all normal. A urine dipstick was clear.
The challenge with such presentations is that the symptoms are vague and could be a feature of common temporary and self-resolving phases in patients with no clear underlying medical condition.
She had not had any investigations for more than 10 years and it appeared sensible to request FBC, ferritin, liver function, renal function, blood sugar, thyroid function, and general inflammatory markers (CRP and ESR).
At the review the following week, the blood results were all normal, apart from minimally out of range LFTs and slightly low sodium (133 mmol/l), as well as mildly raised potassium levels of 5.3 mmol/l.
However, a sitting-standing BP re-check confirmed a significant drop from 120/72 mmHg to 92/60 mmHg, although there were no acute symptoms, such as dizziness.
The BP finding determined postural hypotension, which is defined as a positional difference of at least 20 mmHg.
In the vast majority of patients, the cause of chronically symptomatic low blood pressure and postural hypotension will be situational and harmless - for example, due to poor physical fitness even in young and otherwise well people. But it is important not to miss significant underlying conditions, such as Addison's disease, end-stage malignant disease, or autonomic neuropathy. Also, a close current medication review may reveal an iatrogenic reason.
Hypotension due to cachexia and associated severe fat and protein loss can be caused by malabsorption syndromes and malnutrition (for example, in severe alcoholism), or cardiac failure.
In the elderly of 85 years and older, hypotension (a systolic blood pressure of less than 140 mmHg) appears to be associated with increased mortality, irrespective of an individual’s health status.
Management of postural hypotension may include advice to avoid standing micturition, or to avoid getting up too quickly from a lying or sitting position. In cases of regular vasovagal syncopes there could be a need for medication (prescribed by a specialist), including fludrocortisone (100-200 microgram at night), pyridostigmine or, in some cases, paroxetine, which has been shown to be occasionally helpful. Frequent syncope can have significant implications for a patient's life, including for work and driving.
In this patient, the combination of symptoms and findings of some electrolyte disturbance supported the possibility of Addison's disease (adrenocortical insufficiency due to dysfunction of the adrenal cortex) or another endocrinological disorder.
She was referred for further investigations. For Addison's disease these can include more detailed blood tests - for example, adrenocorticotropic hormone (ACTH), cortisol and renin levels, adrenocortical antibodies (typical sign for autoimmune adrenalitis), and possibly a Synacthen test, or a prolonged ACTH stimulation test. Indeed, the diagnosis of Addison's disease was confirmed for this patient within a few weeks.
Addison's disease, or primary adrenocortical deficiency, is a consequence of the destruction of the adrenal cortex, which means that glucocorticoid, mineralocorticoid, and sex steroid production are all affected. It is a rare condition, with a prevalence of only about one in 10,000 in the UK, but may be increasing. It most commonly affects adults between 30 and 50 years of age. In the past, TB was a likely leading cause for it, whereas now autoimmune adrenalitis accounts for more than 80 per cent of cases.
Far less common causes include various other infections, rare congenital adrenal abnormalities, mechanical infiltration, adrenal trauma, and others. The typical median time for the correct diagnosis after the onset of first symptom is about two years, due to the often non-specific initial signs and symptoms.
In retrospect, this patient presented with many of the possible general features of Addison's disease, such as weakness, gastrointestinal symptoms, fatigue, and low mood. The postural hypotension was an important detail during the re-examination and should always be considered in patients with vague tiredness and dizziness.
Skin features such as hyperpigmentation in Addison's disease, with dull, grey-brown spots, are only a feature of primary hypoadrenalism, due to high ACTH. They are typically seen on mucous membranes, scars, skin folds, and pressure points over the knees and ankles in sun-exposed skin, but may not be present in about 10 per cent of patients.
With lifelong steroid replacement the prognosis is generally good and there is no impact on life expectancy, whereas untreated Addison’s disease can be fatal after an adrenal crisis. The patient should have sufficient information and education to recognise potential emergencies, and carry a steroid card and a MedicAlert bracelet. Addison's disease is associated with an increased incidence of various autoimmune-diseases, such as type 1 diabetes, thyroid and parathyroid disorders, pernicious anaemia, premature ovarian failure, and others, so it requires some vigilance and regular surveillance.
- Dr Jacobi is a GP in York