An Addisonian Crisis following recent Diagnosis and Treatment for Tuberculosis
K Lazarus, H Esdaile, E Nemati, Northwick Park Hospital
Introduction: Addisonís was first described in patients with adrenal tuberculosis (TB) and is the most commonly involved endocrine organ in TB1. It can cause adrenal insufficiency in a number of ways. Here we present a patient who presented with an Addisonian crisis following recent commencement on anti-TB treatment.
A 48-year-old Indian male presented with a 3-day history of fatigue and dizziness, with an acute onset of abdominal pain and vomiting 24 hours previous to presentation. He had recently been diagnosed with TB, and one week previously had commenced anti-TB treatment (rimfampicin, pyrazinadmide, pyridoxine and ethambutol). His initial imaging 2 months previously had shown bilateral adrenal masses, and a CT adrenal showed diffuse enlargement of both adrenals with poor enhancement on the portal venous phase, in keeping with TB adrenalitis.
On further questioning, this patientís wife had commented that his skin appeared darker, with friends and family members asking if he had been abroad. His past medical history included mild depression, and his surgical history included appendectomy. He was taking mirtazapine 45mg OD.
On initial assessment, he had a heart rate of 129 bpm, blood pressure of 111/75 mmHg, a respiratory rate of 29 breaths per minute, and oxygen saturations of 98% on air. He was mildly febrile and had a GCS of 15. Cardiovascular, respiratory and abdominal examinations were unremarkable. An initial VBG showed a pH of 7.405, bicarb of 24.5 mmol/L, lactate of 0.8 mmol/L, glucose of 3.4 mmol/L, potassium of 3.8 mmol/L a sodium of 115 mmol/L. Formal bloods showed a sodium of 117 mmol/L with a plasma osmolality of 243 mOsmol/kg, urine osmolality of 524 mOsmol/kg and urine sodium of 95 mmol/L. The initial post take plan was to give slow intravenous fluids to treat for hypovolaemic hyponatraemia, stop the mirtazapine, and complete the remaining hyponatraemia screen. His sodium dropped further to 113 mmol/L and a short synacthen test was performed; basal cortisol: 132 nmol/L, cortisol at 30 minutes 130 nmol/L and cortisol at 60 minutes 126 nmol/L. His ACTH was 869 ng/L.He was then given hypertonic saline and commenced on hydrocortisone 20mg/10mg/10mg, and his anti-TB medications stopped. His sodium had normalised to 133 mmol/L 4 days later, and fludrocortisone 100mcg once a day was then started. Due to the temporal relationship between starting anti-TB medications and the onset of the Addisonian crisis, it was surmised that rifampicin (a known potent hepatic enzyme inducer) had increased the metabolism of this patientís endogenous cortisol. This precipitated a crisis in a patient with a background of probable subclinical adrenal insufficiency secondary to tuberculosis infiltration.
This was later evidenced by a hydrocortisone day curve several weeks, established on rifampicin and hydrocortisone 20mg + 10mg + 10mg: 09:00 cortisol 59 mmolL, 11:00 cortisol mmol/l, 13:00 244 mmol/L, 15:00 420 mmol/L, 17:00 161 mmol/L.
Discussion: TB and its treatment can affect the adrenal gland in multiple ways; including direct infiltration, and increased cortisol metabolism secondary to enzyme induction from TB treatment. Rifampicin is known to increase cortisol breakdown to 6beta- hydroxycortisol by selectively upregulating liver microsomal cytochrome P450IIIA and this can be achieved by administering for as little as 5 days2.† Our patient had radiological evidence of adrenal infiltration on initial imaging but had not had baseline biochemistry including an early morning cortisol performed.
Learning points from this case therefore include prompt assessment of adrenal reserve prior to commencing anti-TB medications, especially if there is radiological evidence of adrenal involvement, and the need to ensure prompt administration of glucocorticoids in the acute setting.
1. Kelestimur. F. The endocrinology of adrenal tuberculosis: The effects of tuberculosis on the hypothalamo-pituitary-adrenal axis and adrenal function. J Endocrinol. Invest. 27: 3800-386, 2004
2. Ged C et al. The increase in urinary exretion of 6 beta-hydroxycortisol as a marker of human hepatic cytochrome P450IIIA induction. Br J Clin Pharmacol 1989; 28: 373-87.