ACQUIRED BRAIN INJURY STRATEGY
RESPONSE TO CALL FOR EVIDENCE (From Christopher Lane Trust)
1. EXECUTIVE SUMMARY
A significant percentage of ABI-survivors, including the concussed, suffer hormonal deficits, which can cause fatigue, impotence and infertility, brain fog, anxiety, depression, heart problems and osteoporosis. These deficits may take a while to show. Patients are not warned, and are therefore powerless to ask for the correct diagnostic tests. They are likely to be told they have ME, Chronic Fatigue Syndrome, Fibromyalgia or Metabolic Syndrome, which are all symptom clusters with no definitive diagnostic test or cure. By contrast the tests for hypopituitarism are precise, and treatment is simple and usually effective.
Those patients who do discover through their own research what may be wrong with them are often tested inadequately, and hypopituitarism is incorrectly excluded.
The effect of being misdiagnosed with the conditions listed above is to deprive the patient of any hope of getting better. He or she is all too often treated as a malingerer, even by other family members, and it is very isolating to be disbelieved. This may be a contributing factor to the vastly increased suicide rate after brain injury.
Depriving a patient of information in this way is akin to blindfolding a starving man when there is food within reach.
The reluctance to inform patients and medical professionals about this condition may stem from the vast numbers of potential sufferers, the lifelong nature of treatment, and the expense of growth hormone in particular. However, the cost-benefit case of treatment versus non-treatment may not take into account the waste of NHS resources in responding to these patients, who constantly visit their GPs year after year, the unnecessary cost of providing universal credit and other benefits until death, and the failure to enable the patient to make the transition from benefit claimant to tax-payer.
It also has to be remembered that failure to diagnose exposes the patient to the risk of dying suddenly from adrenal crisis because hypoadrenalism (a common feature of hypopituitarism) has not been suspected, or from cardiovascular issues that have not been checked for, not to mention the risk of suicide. Every suicide costs the economy £1.67 million.
Our charity’s recommendations are
- that full information is given to every patient and GP after any degree of head injury including concussion, about possible future symptoms of hypopituitarism
- that the patient is fully informed about the tests necessary to diagnose each pituitary hormone deficiency
2. EVIDENCE
There is a wealth of research demonstrating that the pituitary gland can be damaged after any head injury however mild [1]. The most common effect is growth hormone deficiency [2]. An account of the functions of each pituitary hormone can be found on most pituitary websites [3, 4, 5]. It is sufficient to say here that the effects of hypopituitarism are fatigue, lethargy, generalised weakness, low mood, poor motivation, difficulty with concentration, reduced appetite, unexplained weight loss or gain, dizziness (with hypotension, especially postural). In males, sexual dysfunction, reduced shaving frequency, and in females, oligo-/amenorrhea, reduced axillary or pubic hair [2]. Other complications are infertility [6], cardiovascular disease and osteoporosis [7].
The number of people affected is very large, 50 in every 100,000 patients [8]. BBC’s Inside Health programme aired an estimate of half a million to a million undiagnosed in the UK [9].
There is also much research documenting the efficacy of hormone replacement. People’s cognition and memory improve, their mood improves, their bodies become leaner and more muscular, they have more energy. Their cardiovascular systems become healthier. [10, 11, 12]. People’s fertility and interest in sex returns [13]. A substantial number of diagnosed patients work full time. [14]
Conversely, there is research to show that if hypopituitarism remains undiagnosed, unsuspected hypoadrenalism caused by brain injury results in avoidable deaths. [15] Similarly, research shows the heightened risk of death from cardiovascular issues [16], and diagnosis means that the risk is recognized and managed in time.
3. TESTS
In the experience of people who approach the Christopher Lane Trust, there are three misconceptions among medical professionals that stand in the way of diagnosis:
- That if all the other hormones are normal there is no need to do a stimulation test for growth hormone deficiency. (This test involves giving the patient an injection and then monitoring their growth hormone levels for several hours). However, since growth hormone deficiency is the most common, logic demands that there will be cases where it is the only deficiency. In fact, isolated GH deficiency is not rare [17], and our charity has been made aware of four such cases over the past year.
- That normal IGF-1 levels exclude GH deficiency. However, in fact, the Endocrine Society Clinical Practice Guideline specifically states that “We recommend that a normal IGF-1 level does not exclude the diagnosis of GHD but makes provocative testing mandatory to make the diagnosis of GHD.” [18]
- That a normal result for the short synacthen test excludes cortisol deficiency. However, it only detects adrenal insufficiency of a pituitary origin in three cases out of five. [19]
4. RECOMMENDATIONS
In conclusion, we would advocate that:
- Full information is given to every patient and his or her GP after any degree of head injury including concussion, about possible future symptoms of hypopituitarism.
- The patient is informed about the correct diagnostic tests for every pituitary deficit.
NOTE
If ‘long covid’ is included in the category of acquired brain injury, as it seems it should be, it is worth noting that recent research suggests that the fatigue associated with it has endocrine causes. [20] To quote: “These findings suggest that COVID-19 infection may affect pituitary functions, particularly the HPA and GH axes. These insufficiencies should be kept in mind in post-COVID follow-up. Long-term data are needed to determine whether these deficiencies are permanent or not.” If the deficiencies are permanent, this is all the more reason to address the issue of hypopituitarism with real political urgency.
[1] Schneider HJ et al, Hypothalamopituitary Dysfunction Following Traumatic Brain Injury and Aneurysmal Subarachnoid Haemorrhage: A Systematic Review, 2007, JAMA http://jama.jamanetwork.com/article.aspx?articleid=208915
[2] Tan CL, Alavi SA, Baldeweg SE, et al, The screening and management of pituitary dysfunction following traumatic brain injury in adults: British Neurotrauma Group guidance, J Neurol Neurosurg Psychiatry 2017 http://jnnp.bmj.com/content/88/11/971
[3] https://www.pituitary.org.uk/media/548325/Pituitary-Gland_Sept-17.pdf
[5] https://www.yourhormones.info/glands/pituitary-gland/
[6] Mayo Clinic https://www.mayoclinic.org/diseases-conditions/hypopituitarism/symptoms-causes/syc-20351645
[7] 2 Clinical need and practice | Human growth hormone (somatropin) in adults with growth hormone deficiency | Guidance | NICE (section 2.4)
[8] Fernandez-Rodriguez E et al, Hypopituitarism following traumatic brain injury: determining factors for diagnosis, Front Endocrinol 25 August 2011 doi: 10.3389/fendo.2011.00025 http://www.frontiersin.org/Pituitary_Endocrinology/10.3389/fendo.2011.00025/full The incidence of hypopituitarism following TBI is around 50 patients per 100,000 individuals per year, which results in a high number of patients affected.
[9] Inside Health April 9th transcript http://www.bbc.co.uk/programmes/b01rr37c
[10] Verhelst J, Abs R, Cardiovascular risk factors in hypopituitary, GH-deficient adults, 2009, European Journal of Endocrinology. https://eje.bioscientifica.com/view/journals/eje/161/suppl_1/S41.xml
[11] https://bmcresnotes.biomedcentral.com/articles/10.1186/1756-0500-7-813
[12] Evaluation and Treatment of Adult Growth Hormone Deficiency: an Endocrine Society Clinical Practice Guideline 2011 https://academic.oup.com/jcem/article/96/6/1587/2833853?login=true section 3.4
[13] Fertility in Pituitary Disease, The Pituitary Foundation https://www.pituitary.org.uk/media/633194/Fertility-in-Pituitary-Disease-Oct21.pdf
[14] Brod, M., Pohlman, B., Højbjerre, L. et al. Impact of adult growth hormone deficiency on daily functioning and well-being. BMC Res Notes 7, 813 (2014). https://doi.org/10.1186/1756-0500-7-813
[15] Elshimy G, Chippa V, Jeong JM. Adrenal Crisis. [Updated 2022 Feb 9]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK499968/
[16] Tomlinson JW, Holden N, Hills RK, et al. (February 2001). “Association between premature mortality and hypopituitarism”. Lancet. 357 (9254): 425–31. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)04006-X/fulltext
[17] Popovic V. GH deficiency as the most common pituitary defect after TBI: clinical implications. Pituitary. 2005;8(3-4):239-43. doi: 10.1007/s11102-006-6047-z. PMID: 16508711.GH deficiency as the most common pituitary defect after TBI: clinical implications – PubMed (nih.gov) “GH deficiency is very common in TBI, particularly isolated GHD.”
[18] Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline, Molitch ME et al, The Journal of Clinical Endocrinology & Metabolism, 2011 Evaluation and Treatment of Adult Growth Hormone Deficiency: An Endocrine Society Clinical Practice Guideline | The Journal of Clinical Endocrinology & Metabolism | Oxford Academic (oup.com)
[19] Dorin RI, Diagnosis of Adrenal Insufficiency, 2003, Annals of Internal Medicine, https://pubmed.ncbi.nlm.nih.gov/12899587/ For this review the MEDLINE database was searched from 1966 to 2002 for all English-language papers related to the diagnosis of adrenal insufficiency, and it was found that for diagnosing secondary adrenal insufficiency, the sensitivity of the short synacthen test (here called the cosyntropin test) was 57-61%
[20] Investigation of pituitary functions after acute coronavirus disease 2019 – PubMed (nih.gov)
Joanna Lane BA Hons (Oxon)
CEO Christopher Lane Trust