The process of vaccinating the general population against COVID-19 (type 2 coronavirus that causes severe acute respiratory syndrome) is constantly evolving in terms of knowledge and learning and the eventual need to combine evidence and clinical experience to answer new questions. For this purpose, we present the following case of a 73-year-old woman with a personal history including panhypopituitarism secondary to a pituitary macroadenoma, surgically resected in 1982. Due to recurrence, she subsequently required radiotherapy and a new resection in 2004. Since then, she has been receiving hydrocortisone replacement therapy and thyroid hormone therapy. She has had several Addisonian crises, the last one in 2020 during hospitalisation for COVID-19 pneumonia, which was related to abandonment of treatment and the acute stress condition typical of the infectious process. Bronchial asthma, ischaemic heart disease and chronic kidney disease also stand out in her personal history.
She went to A&E due to an acute deterioration in her state of consciousness, with hypoglycaemia of 63 mg/dl observed at home, which was later resolved with the administration of glucagon. Upon arrival, she was stuporous and in poor general condition, accompanied by hypotension and abdominal pain. The initial history was difficult due to the patient’s confusional state. Treatment was started with intravenous fluid replacement with high-dose glucosamine and hydrocortisone solution, which resulted in a rapid improvement in her condition with the recovery of consciousness and normalisation of blood pressure and blood glucose, and she was admitted to endocrinology.
The patient said she had been taking her usual medication and denied experiencing events that could act as precipitating factors. However, it was found that one day before the onset of symptoms, she was administered the first COVID-19 vaccine (Pfizer) dose, which could have triggered a flu-like subclinical condition since the patient herself described it as intense asthenia, without having increased the doses of hydrocortisone. This makes it the only relevant past history and possible trigger of the current Addisonian crisis. During her admission, a complete analytical study and urine sediment test was performed, without identifying intercurrent infectious processes, in addition to a normal abdominal ultrasound. Given the resolution of her clinical symptoms and the normality of the complementary tests, she was discharged with adjustments to the baseline treatment and specific recommendations to increase the requirements for the second dose of the vaccine.
However, again coinciding with the administration of the said dose, and without identifying another possible trigger, a new hospital admission was required due to symptoms compatible with a new adrenal crisis (low level of consciousness with TBI, hypoglycaemia, hypotension and self-limited fever peak) despite complying with the previous recommendations described, which the family confirmed. Similarly, as before, she subsequently responded favourably to treatment and was discharged.
In the available literature on the BNT162b2 vaccine, they report that local adverse effects are relatively common, mainly after the second dose and in the first two days after the administration of the vaccine. General effects such as arthralgia, asthenia, myalgia and mild-to-moderate respiratory symptoms have also been identified and, less commonly, anaphylactic reactions.1 In addition, some studies suggest a greater immune response and frequency of adverse events with the first dose in patients who have previously had COVID-19 compared to those who have not,2 as was the case with our patient.
The Sociedad Española de Endocrinología y Nutrición [Spanish Society of Endocrinology and Nutrition] reports that patients with adrenal insufficiency do not have a higher risk of adverse effects after vaccination, and recommend its administration than the rest of the general population. Increasing the corticosteroid dose is not specifically recommended.3
According to a survey of professional members of the Pituitary Society, most clinicians do not suggest increasing these requirements with vaccination. However, they may recommend it if the patient develops any symptoms. However, it is recognised that more studies are needed to provide evidence of the need or not of this increase as prophylaxis against possible Addisonian crises.4
In this case, the only situation identified that justifies the adrenal crisis is the previous vaccination, which could have caused a situation of acute stress that, not being supplemented by an extra dose of corticosteroid, caused the aforementioned clinical picture, while knowing that there is great interpersonal variability in people's post-vaccine reaction, ranging from local discomfort to self-limited flu-like symptoms. Considering what has been described in our patient, supervision of an increase in replacement requirements, when indicated, was recommended at discharge, as well as the possibility of a parenteral hydrocortisone regimen before administering future doses of COVID-19 vaccines. In certain situations of acute stress, it is recommended to double or triple the usual dose of corticosteroids in this type of patient, the indication being clear in cases of surgery, severe or moderate infections, vomiting, diarrhoea and fever of more than 38 °C. In milder situations, such as upper respiratory tract infection, fever less than 38 °C and general malaise, it is more debatable and may not be necessary for most patients.5 Likewise, there is no clear indication for increasing the dose before the routine administration of vaccines. More studies are necessary since patients with autoimmune adrenal insufficiency are candidates for routine vaccination to avoid serious infections that can trigger the aforementioned crises.
