Rifampicin induced adrenal crisis in an uncommon setting

Abstract

Adrenal crisis occurs when there is decreased secretions of steroid hormones (mainly cortisol) from the adrenal glands due to varied reasons. It may arise due to a primary adrenal condition or due to decreased hormonal signals from the pituitary secondary to a hypofunctioning pituitary. Hypopituitarism may result due to direct causes like trauma, tumour, infection or it may be due to some vascular insult as seen in Sheehan syndrome. We report an unusual presentation of Sheehan syndrome in the form of life-threatening adrenal crisis precipitated by the usage of rifampicin.

INTRODUCTION

Adrenal crisis occurs when there is decreased secretion of steroid hormones (mainly cortisol) from the adrenal glands due to different reasons. It may arise due to a primary adrenal condition or due to decreased hormonal signals from the pituitary secondary to a hypofunctioning pituitary. Hypopituitarism may result due to direct cause like trauma, tumor, and infection; or it may be due to some vascular insult as seen in Sheehan syndrome. We report an unusual presentation of Sheehan syndrome in the form of life-threatening adrenal crisis precipitated by the usage of rifampicin.

CASE REPORT

A 46-year-old nondiabetic and nonhypertensive female patient presented initially with complaint of central chest pain for 3 months which was insidious in onset, no particular aggravating and relieving factors. She also had weight loss, anorexia, and fatigue for the same duration. A computed tomography (CT) of thorax showed mediastinal lymphadenopathy with no parenchymal involvement. Transbronchial needle aspiration (TBNA) from the mediastinal lymphnodes revealed granulomatuos inflammation. Bronchial washings’ analysis was negative for acid fast bacilli (AFB) stain and culture. A Mantoux test was strongly positive. Based on these investigations, the patient was started on four drug antitubercular therapy (isoniazid, rifampicin, pyrazinamide, and ethambutol). Ten days after starting of antitubercular therapy, patient presented to the emergency department with complaint of increased chest pain and vomiting. On examination, patient was fully conscious with blood pressure of 70/50 mmHg. Adrenal insufficiency was suspected and serum cortisol was sent which was low. A corticotrophin test showed adequate response indicating secondary adrenal insufficiency due to hypothalamopituitary axis (HPA) failure.[1] A CT abdomen done revealed normal adrenals, suggesting involvement of HPA as a cause of adrenal insufficiency. On further enquiry, the patient gave a history of significant postpartum bleeding around 17 years back with difficult lactation in the last childbirth. In the last 2 years she had also noticed gradual loss of axillary and pubic hair and her periods had stopped since last 3 years. Hormone assay revealed low luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, thyroid stimulating hormone (TSH) [Table 1]. Magnetic resonance imaging (MRI) of brain revealed empty sella turcica with nonvisualization of pituitary gland [Figures 1 and 2]. A diagnosis of postpartum hypopituitarism (Sheehan syndrome) was made based on the above history and investigation findings. Patient was put on steroids (intravenous hydrocortisone followed by oral prednisolone) to which she responded. The chest pain and vomiting abated and hypotension was reversed. She subsequently recovered completely. Steroids and antitubercular drugs were continued.

Table 1.

Hormonal profile of the patient

Figure 1.

Magentic resonance imaging (MRI) brain (sagittal section) showing empty sella turcica

Figure 2.

MRI brain (coronal section) showing empty sella

DISCUSSION

Sheehan syndrome or postpartum hypopituitarism is a cause of hypopituitarism following significant blood loss during childbirth resulting in pituitary necrosis and subsequent pituitary dysfunction.[2,3] Women with Sheehan syndrome have varying degrees of hypopituitarism ranging from selective hormonal deficiency to full-blown panhypopituitarism.[4] Commonly the syndrome presents as difficulty with lactation or disturbance in menstruation (amenorrhoea or oligomenorrhoea) due to decreased pituitary secretion of prolactin and sex hormones, respectively. In some patients there may be manifestations of secondary hypothyroidism or growth hormone deficiency due to deficiency of the respective hormones. In some cases Sheehan syndrome may present with secondary adrenal insufficiency following acute stressors like surgery or infection.[2] Rifampicin is an antibiotic of the rifamycin group which is used commonly as an antitubercular agent. It is also a potent microsomal enzyme inducer especially cytochrome P-450 which can lead to enhanced metabolism of different drugs as well as some hormones like cortisol.[5] The patient in our case had subclinical hypopituitarism following postpartum hemorrhage which resulted in difficulty in lactation, loss of axillary and pubic hair, weakness, and lethargy. She was diagnosed as a case of probable pulmonary tuberculosis and started on standard antitubercular drugs including rifampicin. Administration of rifampicin lead to increased cortisol metabolism and precipitation of adrenal crisis. Review of the literature revealed only one similar case report. We believe this is the second such case report in world literature which prompted us to report it.[6] The important highlights of the case report being that after starting rifampicin if a patient presents with features of nausea, vomiting, weakness, and hypotension; one should consider a diagnosis of adrenal insufficiency. Commonly adrenal insufficiency in a patient with tuberculosis is due to tubercular involvement of the adrenals, but very rarely the patient might have concomitant pituitary insufficiency. Administration of enzyme-inducers like rifampicin might lead to precipitation of adrenal crisis in this scenario. Meticulous history taking and appropriate investigations will clinch the diagnosis in such a situation. Steroid replacement in appropriate dose is of paramount importance as a preventive and therapeutic measure.