Quick tip; it vital not to delay initiation of treatment in unwell patients if adrenal insufficiency suspected – the diagnosis can always be established later
The adrenal cortex secretes cortisol and androgens (under control of pituitary ACTH) as well as aldosterone (under control of the renin-angiotensin-aldosterone system).
Adrenal insufficiency may be primary (due to destruction/dysfunction of the adrenal gland itself), secondary (due to inadequate ACTH from the pituitary) or tertiary (due to pituitary suppression from exogenous steroids).
Primary adrenal insufficiency causes deficiency of cortisol, androgens and aldosterone; secondary and tertiary insufficiency cause deficiency of cortisol and androgens alone.
Causes of adrenal insufficiency
Symptoms of adrenal insufficiency are non-specific and include
Adrenal crisis is a life-threatening manifestation of adrenal insufficiency characterised by haemodynamic shock.
Management of adrenal crisis
Prevention of adrenal crisis
SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute adrenal insufficiency (adrenal crisis) in adult patients (2016) URL: https://ec.bioscientifica.com/view/journals/ec/5/5/G1.xml
Guidelines for the management of glucocorticoids during the peri‐operative period for patients with adrenal insufficiency
Guidelines from the Association of Anaesthetists, the Royal College of Physicians and the Society for Endocrinology UK (2020) URL: https://onlinelibrary.wiley.com/doi/full/10.1111/anae.14963
Quick tip - 40-45% of calcium circulates bound to albumin, so disorders of albumin can cause apparent (false) hypo or hypercalcaemia – calcium levels should therefore always be adjusted for albumin concentration.
Serum calcium is regulated by parathyroid hormone (PTH) and vitamin D (dependent on sufficient dietary intake/sun exposure).
High serum calcium is usually (~90% of the time) caused by primary hyperparathyroidism (PTH excess) or malignancy.
Symptoms depend on the degree of hypercalcaemia, and include polyuria and thirst, constipation, bony pains, weakness and (less commonly) delirium. Hypercalcaemia in the long term is associated with renal stones and osteoporosis.
Causes of hypercalcaemia:
Useful to stratify as:
PTH-dependent (PTH inappropriately high or mid-high normal when calcium is high)
PTH-independent (PTH appropriately suppressed or low-normal when calcium is high)
Quick tip – ensure vitamin D is well replaced before giving parenteral bisphosphonates or denosumab for osteoporosis, and before head and neck surgery, to avoid crashing hypocalcaemia
Serum calcium levels are controlled by parathyroid hormone (PTH) and vitamin D, as well as by calcium and phosphate status.
Hypocalcaemia can therefore be caused by:
Calcium in circulation is bound to albumin, so we adjust total calcium levels for albumin. In cases of acid-base disturbance, calcium binding to albumin may be affected so an ionised calcium may be more accurate, but is rarely indicated.
Causes of hypocalcaemia:
Like hypercalcaemia, it is useful to consider PTH-dependent and independent causes. The usual response to hypocalcaemia would be a rise in PTH – if this does not occur it suggests a parathyroid problem.
PTH low or normal – primary hypoparathyroidism
Symptoms and signs:
Causes may be clinically obvious e.g. post thyroid surgery. In patients with vitamin D or PTH resistance there is usually childhood onset and a family history.
SOCIETY FOR ENDOCRINOLOGY ENDOCRINE EMERGENCY GUIDANCE: Emergency management of acute hypocalcaemia in adult patients. (2016) URL: https://ec.bioscientifica.com/view/journals/ec/5/5/G7.xml
NICE Clinical Knowledge Summaries. Vitamin D in adults – treatment and prevention. URL: https://cks.nice.org.uk/vitamin-d-deficiency-in-adults-treatment-and-prevention#!scenario
Quick tip – never hold back hydrocortisone treatment in an emergency in order to secure a diagnosis of adrenal insufficiency. That can always be done later. A blood sample taken before hydrocortisone can be analysed afterwards for cortisol (and ideally ACTH).
Cortisol is the main glucocorticoid hormone. >95% in circulation is bound to CBG (cortisol binding globulin), however it is the free unbound hormone that is active.
We measure total serum cortisol levels rather than the free active component as this is very difficult to do outside the research setting.
There are many caveats with measuring plasma cortisol levels and a single random cortisol measurement may not be helpful in proving sufficiency or insufficiency. Patients with cortisol deficiency or excess may have a cortisol level within the “normal range” at certain times of the day. It is for these reasons that we usually investigate suspected cortisol disorders with dynamic function testing (e.g. synacthen test, dexamethasone suppression test) to determine if cortisol levels are appropriate to the circumstance (section on DFTs to follow).
The main use of a plasma cortisol measurement in the hospital setting is in excluding adrenal insufficiency. We might think about this in the investigation of unexplained hyponatraemia or weight loss, for instance, or in a hypotensive patient in a sample taken before we administer empirical hydrocortisone.
Random plasma levels of cortisol have no real use if cortisol excess is suspected (including patients with features of glucocorticoid excess such as obesity and diabetes, or in patients with adrenal or pituitary masses).
Factors influencing cortisol levels:
If cortisol insufficiency suspected:
If cortisol insufficiency confirmed:
Cortisol excess suspected: