A 54-year-old male, diagnosed with HIV-1 infection 8 years earlier, was well controlled on Atripla (efavirenz 600 mg/emtricitabine 200 mg/tenofovir disoproxil 245 mg) with CD4 count 370 cells/mm3 and viral load <40 copies/ml presented with fever, weight loss and shortness of breath. Chest imaging found a large left pleural effusion with left lower lobe consolidation. Fully sensitive M. tuberculosis was isolated from pleural specimens. He responded to standard anti-tuberculosis treatment (rifampicin, isoniazid, pyrazinamide and ethambutol). Atripla was continued with additional efavirenz 200 mg o.d. to overcome predicted rifampicin-efavirenz drug interaction. After 2 months, he developed marked reduction in libido with erectile dysfunction. Investigations found serum total testosterone 11 nmol/l, SHBG 170 nmol/l, calculated free testosterone 60 pmol/l, LH 14 IU/ml and FSH 15 IU/ml. Efavirenz has a direct oestrogenic effect by modulating oestrogen receptors [], and this effect may have been exacerbated by SHBG elevation (HIV infection, anti-tuberculosis treatment and ART) reducing free testosterone concentrations, despite normal total levels. After additional efavirenz was discontinued, SHBG returned to normal and his clinical symptoms fully resolved.
A 49-year-old man presented with sudden confusion and headache. He was diagnosed HIV-positive (CD4 220 cells/mm3, viral load 3898 copies/ml) with acute kidney injury and CMV viraemia. Computerised tomography (CT) brain imaging was normal. He received once daily lamivudine 300 mg, darunavir 800 mg and ritonavir 100 mg with raltegravir 400 mg b.d. He developed symptomatic hypotension. Testosterone was <0.3 pmol/l with biochemical features of panhypopituitarism with cortisol <25 nmol/l, free thyroxine 4.6 pmol/l, TSH <0.05 IU/l, prolactin <10 mIU/l, LH 1.2 IU/l and FSH <0.5 IU/l. Cerebrospinal fluid (CSF) analysis revealed a raised protein (0.66 g/l) and negative microscopy. MR imaging found evidence of subacute haemorrhage in the pituitary gland, with no evidence of pituitary tumour, suggesting direct haemorrhage into the gland, which is unusual (Fig. ). The working diagnosis was CMV infection of the pituitary gland causing haemorrhage []. His hypopituitarism was treated by appropriate endocrine replacement with hydrocortisone, levothyroxine and testosterone.