Introduction: Megestrol acetate is a synthetic progestin that binds to the glucocorticoid receptor.  Megestrol is a modified derivative of the naturally occurring hormone progesterone, indicated primarily to stimulate appetite for the treatment of significant, inexplicable weight loss in HIV/AIDS patients and anorexia or cachexia syndrome. It has an inherently greater potential to suppress the HPA axis than to induce glucocorticoid-like clinical effects. We present here an interesting case of megestrol-induced HPA axis suppression leading to chronic hyponatremia.

 

Case Presentation: A 60-year-old malnourished female with multiple comorbidities including Chronic obstructive pulmonary disease and non-insulin-dependent diabetes mellitus presented with shortness of breath with productive cough and worsening generalized weakness for the past 1 week. She was afebrile and hemodynamically stable and saturating on 3L.  On physical examination, she was alert oriented x3 with intermittent confusion; mild respiratory distress. 

Initial investigations demonstrated leukocytosis 14.2, hemoglobin 11.0, sodium 117, chloride 75.  Further evaluation for hyponatremia showed urine osmolality 224 and urine sodium 49.  Morning cortisol, TSH, and free T3 levels were reduced. Cosyntropin test demonstrated cortisol levels of 14.2 at the half-hour indicating adrenal insufficiency. The chest x-ray was normal. 

 

The patient was started on normal saline due to suspicion of hypovolemic hyponatremia. Further review of her medical records revealed chronic hyponatremia with baseline sodium in mid 120s. Medication review revealed the use of megestrol acetate 40 mg twice daily is known to cause HPA axis suppression leading to hyponatremia.  Megestrol was discontinued due to suspicion of being the culprit drug for HPA suppression and adrenal insufficiency.  

 

The patient’s sodium improved to 127 with normal saline and discontinuation of megestrol. Hyponatremia was attributed to megestrol-induced HPA suppression causing hyponatremia. COPD exacerbation was concomitantly managed with albuterol inhalation, antibiotics, oxygen and oral prednisone during the hospital stay. 

 

Working Diagnosis: Megestrol-induced hyponatremia

 

Outcome and Follow-up: Our patient had chronic hyponatremia related to HPA axis suppression related to long term megestrol use. After discontinuation of megestrol, her sodium improved and has been within the normal range on follow-up on 2 different occasions after discharge. The concern of SIADH was ruled out following significant improvement in the sodium levels after discontinuation of megestrol and treatment with steroids. These point to a high probability of hyponatremia being related to the HPA axis suppression caused by megestrol.  

Our patient highlights a rarely thought of clinical association between megestrol and hyponatremia related to HPA suppression. We suggest monitoring basic metabolic profile in patients who are on long-term megestrol acetate. Patients should be advised to stop megestrol if they’re known to have HPA axis suppression.  Drugs that could potentially cause SIADH and hyponatremia should be cautiously used in patients taking Megestrol acetate.