Brain Injury Study Guide – Hypopituitarism
29 June 2018
The second in our series of in depth study guides brought to you by our in house experts.
Hypopituitarism is very common after brain injury and is often misdiagnosed.
What is hypopituitarism?This means the pituitary gland is not functioning properly. The pituitary gland is the "master gland" that controls all the other hormonal glands within the body. It is a small gland on a stalk sitting in the middle of the brain. Unfortunately, its position, anatomy and blood supply make it vulnerable to traumatic brain injury. The gland is split into two parts – the anterior pituitary and the posterior pituitary. The posterior pituitary produces a hormone called AVP (arginine vasopressin) which controls the water balance in the body. If this function goes wrong it is called diabetes insipidus (which should not be confused with diabetes mellitus or "sugar" diabetes. It is an entirely different disorder). Shortage of this hormone means that the person will produce large volumes of dilute urine – often over three litres per day. This obviously leads to thirst and dehydration. It is very common in the immediate, post-injury phase and it is often only seen in the acute hospital. It is relatively straightforward to diagnose and easily treated – by simply drinking more water. However, if the problem is really severe then there are medications that can correct the hormonal deficit.
In the longer term, it is the hormones in the anterior pituitary gland that have such a major impact on daily life. The anterior pituitary gland produces hormones that control sexual function, growth, steroid production and thyroid production. All these deficiencies have their own particular pattern of deficits which are described further below.
Can we predict who gets hypopituitarism? The answer is not really. It tends to occur in younger men but there again brain injury also occurs in younger men. The type of brain injury is no real help although more severe injury does lead to a higher risk of hypopituitarism. A fracture of the basal part of the skull also leads to a higher risk. A warning sign is diabetes insipidus occurring in the acute phase which gives rise to a higher risk of other pituitary problems occurring later after the injury.
The overall risk of hypopituitarism is surprisingly high and it is said that somewhere between 30-50% of people after a severe brain injury will develop some hypopituitary symptoms at some stage. It is also important to note that it can occur late after the injury, although 75% of people who get the problem have developed it within the first year.However, this obviously means that 25% will develop the problem after one year which in turn means that the link between the symptoms and the brain injury is sometimes not made.
So what are the symptoms? The problem is that the symptoms of hypopituitarism can be rather vague and also commonly occur after brain injury even in those who do not have pituitary problems. Overall, the commonest difficulty is tiredness and as documented in another fact sheet in this series, tiredness and easy fatigability are very common after brain injury. It is important to have a high index of suspicion and if someone has particular problems with fatigue after brain injury then they should certainly be checked for hypopituitarism.
To some extent the exact symptoms depend on which hormones are affected.The commonest to be affected is growth hormone.As the name implies growth hormone is responsible for growth in children and lack of the hormone will often produce growth failure. However, lack of the hormone can also lead to problems in adults.These problems largely focus on decreased energy with tiredness, decrease in muscle mass and an increase in fat mas and also depression.Once again, all these are common difficulties after brain injury. A deficit of the sexual hormones (FSH and LH) will cause loss of libido and in women menstrual cycle problems and in men erectile problems. There can be a loss of fertility in both sexes. Once again, the situation is compounded by lack of energy and depression.
These same symptoms also occur with a deficit of ACTH which controls steroid production. Fatigue, weight loss, anorexia (poor appetite) and metabolic problems are common. A low thyroid from a lack of the thyroid stimulating hormone (TSH) in hypopituitarism can also cause tiredness as well as coldness, constipation, hair loss, dry skin, hoarse voice and cognitive "slowness", weight gain and depression.
Thus, whilst there are some specific symptoms, most of the problems of hypopituitarism are rather non-specific and common in brain injury in any case.This comes back to the point that a doctor, case manager or other health professional needs to have a high index of suspicion. There is certainly a case to be made that everyone after brain injury, certainly at the severe end of the spectrum, should undergo pituitary function testing. The importance of testing the pituitary is that if a hormonal deficit can be determined then it is easily corrected by hormone replacement. It is clearly vital to detect and treat the treatable.
How do we test for pituitary deficit? The main point here is that a simple blood test to check the level of hormones in the blood is inadequate. Sometimes low hormones in the blood stream can be a pointer but often the hormone levels are in the normal range but are unable to respond to the necessary peak in concentration at times of stress. Thus to diagnose hypopituitarism properly, the gland has to be put under stress and the hormones measured before and after the stressor to see if the gland is able to respond. There are a number of provocative tests that can be given and one, for example, is to give the individual a small dose of insulin which lowers the blood sugar and as a result the pituitary hormones should rise in response. There are other tests available. However, the basic rule is that if there is any suspicion of hypopituitarism then the individual must be referred to the local endocrinology department. The testing is simple but does involve the person coming into a day unit to have blood taken over a period of a few hours before and after the provocative stressor. This is marginally inconvenient but nevertheless is the only proper way to diagnose the condition.
Once a hormone deficit is determined then it is straightforward to prescribe replacement therapy, such as a growth hormone, thyroxine, oral steroids, etc. This treatment can produce a complete improvement in those particular symptoms. This is clearly a great result for those who may have a very low quality of life as a result of tiredness or depression, etc. Sometimes there is only a partial improvement after correcting the hormonal deficit and this probably means that whilst the low pituitary hormone had some role in the symptoms, the brain injury itself also played a part in the symptomatology. However, any improvement is clearly better than no improvement.
In summary, hypopituitarism after brain injury, particularly severe injury, is very common. It can produce a range of symptoms that are rather non-specific and common in any case in the context of brain injury. There needs to be a high index of suspicion of hypopituitarism and the individual must be referred to an endocrinology department to undergo proper testing. The results and treatment are often very satisfactory and can produce significant benefits and improved quality of life.
References for Future Reading
Norwood KW, Deboer MD, Gurka MJ, et al. Traumatic brain injury in children and adolescents: surveillance for pituitary dysfunction. Clin Pediatr (Phila) 2010; 49(11): 1044-9
Blair JC. Prevalence, natural history and consequences of posttraumatic hypopituitarism: a case for endocrine surveillance. Br J Neurosurg 2010; 24(1): 10-7
Quinn M, Agha A. Post-traumatic hypopituitarism – who should be screened, when, and how? Front Endocrinol (Lausanne) 2018; Feb 2;9:8. doi: 10.3389/fendo.2018.00008. eCollection 2018
Zaben M, El Ghoul W, Belli A. Post-traumatic head injury pituitary dysfunction. Disabil Rehabil 2013; 35(6): 522-5