Age: 21.0
Sex: M
Vaccine: DTAP, FLUX
Symptoms: Blood testosterone decreased, Blood testosterone free decreased, Blood thyroid stimulating hormone normal, Bradycardia, Cold sweat
Clinical narrative: Adrenal crisis/acute adrenal insufficiency; Tingling and numbness of feet and toes; Tingling and numbness of feet and toes; This literature case from was retrieved on 20-Oct-2021 from Vaccine Adverse Event Reporting System (VAERS) (reference number: 1751724-1) with additional information received on the same day (being processed together) and concerned a 21-year-old, male patient.  The patient's concurrent conditions included euthyroid sick syndrome and underlying autoimmune Addison's disease/undiagnosed autoimmune adrenalitis. The patient's concomitant medications were not reported.  The primary objective of this study was to recognize adrenal crisis (AC) in patients without known adrenal insufficiency after vaccinations.   On an unknown date, in preparation for school, the patient was vaccinated with influenza virus vaccine polyvalent (brand not specified; dose, route of administration and anatomical location: not reported) for prophylaxis. The batch number was not reported.  On the same day, the patient was vaccinated with non-company co-suspect DTaP (diphtheria vaccine toxoid, pertussis vaccine acellular, tetanus vaccine toxoid; dose, route of administration and anatomical location: not reported) for prophylaxis. The batch number was not reported.  On an unknown date, two days after receiving with influenza virus vaccine polyvalent and co-suspect DTaP, the patient experienced generalized body aches, fatigue and malaise.   On an unspecified date, five days after vaccinations, the patient experienced mid-abdominal discomfort associated with scant vomiting with associated decreased appetite and fluid intake.  On an unspecified date, six days after vaccinations, the patient experienced tingling and numbness of feet and toes.  On an unspecified date, one week after receiving influenza virus vaccine polyvalent and non-company co-suspect DTaP, the patient presented to the emergency room (ER). His family had brought him to the hospital as he had been lethargic and appeared cyanotic. The patient denied fever, chills, rash, joint swelling, joint pain, neck stiffness or pain, sore throat, sinus drainage or pressure, urinary complaints, or bowel changes. He also denied recent travel or sick contacts. In the ER, the patient was lethargic, bradycardic with a heart rate of 30 beats per minute and had low blood pressure at 90/60 mmHg. On examination, he had a cold, as well as clammy skin that was mottled in color. Initial laboratory tests were: haemoglobin was 16.9 g/dL (normal range 13.7-17.5), sodium was 102 mmol/L (normal range 136-145), potassium was 6.2 mmol/L (normal range 3.5-5.1), aspartate aminotransferase was (AST) 299 U/l (normal range 15-37) and alanine aminotransferase was (ALT) 124 U/l (normal range 30-65). Additionally, the patient's urine analysis was unremarkable. He was transferred to the intensive care unit (ICU) and started on fluids and given a prophylactic dose of ceftriaxone. A cortisol level was drawn, and the patient was given a dose of dexamethasone for the possibility of adrenal crisis (AC) in light of concurrent hyponatremia, hyperkalaemia, hypotension, and hypothermia. The patient's blood pressure, heart rate, and coloration improved. Due to this positive response, he was started on intravenous (IV) hydrocortisone. Subsequent laboratory tests were: cortisol was 0.69 mcg/dL (normal range 4.3-22.4), adrenocorticotropic hormone (ACTH) was >2000 pg/mL (normal range 7.2-63.3), dehydroepiandrosterone sulfate (DHEA) was <15 mcg/dL (normal range 80.0-560.0), total testosterone was 200 ng/dL (normal range 264-916), free testosterone was 0.8 pg/mL (normal range 9.3-26.5), 21-hydroxylase antibodies were 40 U/mL (normal range <1), thyroid-stimulating hormone (TSH) was 5.25 mcInU/mL (normal range 0.36-3.74) and thyroxine (T4) was 1.62 ng/dL (normal range 0.89-1.76). The low cortisol level prior to the treatment combined with improvement in clinical status following glucocorticoid treatment was consistent with adrenal crisis. Diagnostic laboratory testing that demonstrated an elevated ACTH along with a decreased dehydroepiandrosterone sulfate (DHEA), total testosterone, and free testosterone, and elevated 21-hydroxylase antibodies were consistent with autoimmune Addison's disease. Thyroid-stimulating hormone (TSH) that was slightly elevated, with a normal T4, was suggestive of euthyroid sick syndrome. Computed tomography (CT) of abdomen showed no gross adrenal enlargement or abnormalities. Blood cultures did not grow any organisms. With continued treatment with steroids, the patient's severe hyponatremia and other electrolyte abnormalities were corrected.   On an unspecified date the patient was discharged from hospital. On discharge, the endocrinologist recommended starting the patient on maintenance mineralocorticoid. The patient was educated on the course of the disease and the need for exogenous steroids for maintaining good health.  On an unspecified date, the patient recovered from the events of 'adrenal crisis', 'tingling' and 'numbness in feet'.    In conclusion, acute adrenal insufficiency, also known as adrenal crisis, was a rare but known life-threatening condition. Patients with adrenal insufficiency may go undiagnosed until they have significant stressors inducing like in this case where adrenal crisis was induced by influenza and DTaP vaccination. All vaccines are known to cause fever, fatigue, and gastrointestinal disturbances by themselves, thereby making it difficult to diagnose AC. As infections are a major precipitant of AC, receiving future routine vaccinations should not be barred in patients with AI or those who have AC secondary to vaccinations.   The reporter assessed the events as related to influenza virus vaccine polyvalent and DTaP. Adrenal crisis was induced by influenza and DTaP vaccination in a patient without a known history of adrenal insufficiency. It was also considered that as the patient had received two vaccines simultaneously, this potentially increased the stressor burden.   The event of 'adrenal crisis' was assessed as serious due to hospitalization, medical significance and life-threatening condition. The events of 'tingling' and 'numbness in feet' were assessed as serious due to hospitalization.  Company Comment: A 21-year-old, male patient was vaccinated with the suspect product influenza virus vaccine polyvalent and non-company co-suspect DTaP vaccine. Within five days the patient developed abdominal discomfort and vomiting with associated decreased appetite and fluid intake. The patient developed paraesthesia and numbness six days after vaccination. After seven days the patient presented at the emergency room with sings and symptoms of adrenal insufficiency (AI). The patient was given a dose of dexamethasone for the possibility of adrenal crisis (AC) with improvement of blood pressure, heart rate, and coloration. Performed laboratory and diagnostic findings were consistent with underlying Addison's disease and euthyroid sick syndrome both of which confound causality. Additionally, causality was confounded by concurrent administration of DTaP vaccine increasing the stressor burden. As per reporter patients with AI may go undiagnosed until they have significant stressors inducing an AC. Therefore, causality for the event adrenal crisis is assessed as possibly related although confounded by underlying condition. Causality for the events paraesthesia and numbness is assessed as possibly related based on plausible temporal relationship.; Reporter's Comments: The reporter assessed the events as related to influenza virus vaccine polyvalent and DTaP. Adrenal crisis was induced by influenza and DTaP vaccination in a patient without a known history of adrenal insufficiency. It was also considered that as the patient had received two vaccines simultaneously, this potentially increased the stressor burden.; Sender's Comments: A 21-year-old, male patient was vaccinated with the suspect product influenza virus vaccine polyvalent and non-company co-suspect DTaP vaccine. Within five days the patient developed abdominal discomfort and vomiting with associated decreased appetite and fluid intake. The patient developed paraesthesia and numbness six days after vaccination. After seven days the patient presented at the emergency room with sings and symptoms of adrenal insufficiency (AI). The patient was given a dose of dexamethasone for the possibility of adrenal crisis (AC) with improvement of blood pressure, heart rate, and coloration. Performed laboratory and diagnostic findings were consistent with underlying Addison's disease and euthyroid sick syndrome both of which confound causality. Additionally, causality was confounded by concurrent administration of DTaP vaccine increasing the stressor burden. As per reporter patients with AI may go undiagnosed until they have significant stressors inducing an AC. Therefore, causality for the event adrenal crisis is assessed as possibly related although confounded by underlying condition. Causality for the events paraesthesia and numbness is assessed as possibly related based on plausible temporal relationship.