Sex: M
Vaccine: DTAP, FLUX
Symptoms: 21-hydroxylase deficiency, Abdominal discomfort, Addison's disease, Adrenocortical insufficiency acute, Alanine aminotransferase increased
Clinical narrative: Adrenal crisis; decreased appetite; decreased fluid intake; Lethargic; Cyanotic; bradycardic; low blood pressure; Cold; clammy skin; Skin mottled in color; Hyponatremia; Hyperkalemia; Hypothermia; low cortisol level; autoimmune Addison's disease; euthyroid sick syndrome; mid-abdominal discomfort; vomiting; tingling; numbness of feet and toes; generalized body aches; Fatigue; Malaise; This case was reported in a literature article and described the occurrence of adrenal crisis in a 21-year-old male patient who received Flu unspecified (Influenza vaccine) for prophylaxis.  Co-suspect products included DTPa (DTaP vaccine) for prophylaxis.   On an unknown date, the patient received Influenza vaccine and DTaP vaccine. On an unknown date, less than a week after receiving Influenza vaccine and DTaP vaccine, the patient experienced adrenal crisis (serious criteria hospitalization and GSK medically significant), general body pain (serious criteria hospitalization), fatigue (serious criteria hospitalization), malaise (serious criteria hospitalization), abdominal discomfort (serious criteria hospitalization), vomiting (serious criteria hospitalization), decreased appetite (serious criteria hospitalization), oligodipsia (serious criteria hospitalization), tingling (serious criteria hospitalization), numbness in feet (serious criteria hospitalization), lethargy (serious criteria hospitalization), cyanosis (serious criteria hospitalization), bradycardia (serious criteria hospitalization and GSK medically significant), low blood pressure (serious criteria hospitalization), cold (serious criteria hospitalization), clamminess (serious criteria hospitalization), mottled skin (serious criteria hospitalization), hyponatremia (serious criteria hospitalization), hyperkalemia (serious criteria hospitalization and GSK medically significant), hypothermia (serious criteria hospitalization and GSK medically significant), cortisol decreased (serious criteria hospitalization), addison's disease (serious criteria hospitalization and GSK medically significant) and euthyroid sick syndrome (serious criteria hospitalization). The patient was treated with ceftriaxone, dexamethasone, hydrocortisone and glucocorticoids nos (Glucocorticoid). On an unknown date, the outcome of the adrenal crisis, abdominal discomfort, decreased appetite, oligodipsia, lethargy, cyanosis, bradycardia, low blood pressure, cold, clamminess, mottled skin, hypothermia, addison's disease and euthyroid sick syndrome were unknown and the outcome of the general body pain, fatigue, malaise, vomiting, tingling, numbness in feet, hyponatremia and hyperkalemia were recovered/resolved and the outcome of the cortisol decreased was recovering/resolving.   The reporter considered the adrenal crisis, general body pain, fatigue, malaise, abdominal discomfort, vomiting, decreased appetite, oligodipsia, tingling, numbness in feet, lethargy, cyanosis, bradycardia, low blood pressure, cold, clamminess, mottled skin, hyponatremia, hyperkalemia, hypothermia, cortisol decreased, addison's disease and euthyroid sick syndrome to be related to Influenza vaccine and DTaP vaccine.  Additional details were reported as follows: This case was reported in a literature article and described the occurrence of adrenal crisis (AC) in a 21-year-old male patient, who was vaccinated with unspecified Influenza vaccine and unspecified Diphtheria, Tetanus, and acellular Pertussis (DTaP) vaccine (manufacturer unknown) for prophylaxis. No information on patient's medical history or family history or concurrent condition or concomitant medication was provided. On an unspecified date, the patient received unspecified Influenza vaccine and unspecified Diphtheria, Tetanus, and acellular Pertussis (DTaP) vaccine (Route and site of administration unknown; batch number not provided; dosage unknown for both) in preparation for school. The age of vaccination was not provided. On an unspecified date, 1 week after the vaccination, the patient presented to the emergency room (ER) with complaints of generalized body aches, fatigue, and malaise for five days. The patient reported mid-abdominal discomfort associated with scant vomiting for two days with associated decreased appetite and fluid intake. The patient endorsed tingling and numbness of feet and toes for one day. The patient's family had brought the patient to the hospital as the patient 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. The patient 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, the patient had a cold, as well as clammy skin that was mottled in color. Initial laboratory testing at the time of admission showed hemoglobin 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 (AST) was 299 U/L (normal range: 15-37) and alanine aminotransferase (ALT) was 124 U/L (normal range: 30-65). Additionally, the patient's urine analysis was unremarkable. The patient 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 AC in light of concurrent hyponatremia, hyperkalemia, hypotension and hypothermia. The patient's blood pressure, heart rate, and coloration improved. Due to this positive response, the patient started on intravenous (IV) hydrocortisone. Subsequent laboratory testing showed cortisol was 0.69 mcg/dL (normal range: 4.3-22.4), adrenocorticotropic hormone (ACTH) was more than 2000 pg/mL (normal range: 7.2-63.3), dehydroepiandrosterone sulfate (DHEA) was less than 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 was 40 U/mL (normal range: less than 1), thyroid-stimulating hormone (TSH) was 5.25 mcInU/mL (micro IU/mL) (normal range: 0.36-3.74) and 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 AC. Further diagnostic laboratory testing demonstrated an elevated Adreno corticotropic hormone (ACTH) along with a decreased dehydroepiandrosterone sulfate (DHEA), total testosterone, and free testosterone. 21-hydroxylase antibodies were elevated, consistent with autoimmune Addison's disease. Thyroid-stimulating hormone (TSH) was slightly elevated, with a normal T4, suggestive of euthyroid sick syndrome. CT abdomen done 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. The endocrinologist recommended starting the patient on maintenance mineralocorticoid on discharge. This case was considered as serious due to Hospitalization. The authors commented, "Our patient did not have a known history of AI prior to admission, nor did he endorse any symptoms prior to his vaccination. However, we speculate that our patient had underlying undiagnosed Adrenal insufficiency (AI). This may be attributed to the already vague symptoms of AI, such as fatigue, weight loss, and loss of appetite, which develop slowly over months. In itself, AI is fairly rare with studies reporting the prevalence ranging from 35-60 per million, thereby making the diagnosis easier to be overlooked. Patients with AI may go undiagnosed until they have significant stressors inducing an AC. In 70-90% of cases of AI, the primary etiology was determined to be autoimmune adrenalitis. As our patient had antibodies against 21-hydroxylase, we believe he had underlying autoimmune Addison's disease. It is important during the time of diagnosis to also assess for other endocrine disorders, as they can occur concurrently and further precipitate AC. Commonly associated disorders include thyroid disease, diabetes mellitus, and, in women, premature ovarian insufficiency. We believe our case is the first presentation of AC induced by influenza and DTaP vaccination in a patient without a known history of AI. Potential causes of AC are usually well-known, with ongoing debates of less common etiologies and arguments around what constitute a significant stressor. Some data suggests that even strong emotional states can precipitate AC. We also consider that our patient had received two vaccines simultaneously, potentially increasing the stressor burden. Typically, for patients with a known history of AI who present with fatigue and gastrointestinal disturbances along with hypotension, AC should be high on the differential. All vaccines are known to cause fever, fatigue, and gastrointestinal disturbances by themselves, thereby making it difficult to diagnose AC. In patients such as ours without a known history of AI who present with shock resistant to vasopressors, AC should be ruled out. Regardless of a clear diagnosis, empiric treatment with steroids should take priority over confirmatory testing in cases of suspected AC. As our patient did not have any prior history, he was educated on the course of the disease and the need for exogenous steroids for maintaining good health. 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 authors concluded, "This case demonstrates that vaccines can play the role of a stressor, potentially significant enough to induce AC. We recommend future studies to assess the incidence of AC in patients with and without known AI after vaccinations. We also believe that further studies on preventing AC after vaccinations and the role of stress dose steroids in preventing AC as well as the efficacy of the vaccines are required."