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CASE REPORT |
Department of Internal Medicine, VU University Medical Center, PO Box 7075, 1007 MB Amsterdam, The Netherlands
(Correspondence should be addressed to P W B Nanayakkara; Email: p.nanayakkara{at}vumc.nl)
Abstract
Objective: To describe a patient with cocaine-induced panhypopituitarism associated with human neutrophil elastase-anti-neutrophil cytoplasmic antibodies (HNE-ANCA).
Case: A 41-year-old man presented with extreme fatigue, cold intolerance and anorexia with 20 kg weight loss in the last 6 months. His medical history was unremarkable. He snorted cocaine twice a week during the last 6 years. On examination, we saw a pale and skinny man, with a normal blood pressure. Because of the severity of symptoms central hypothyroidism was suspected and very low values of TSH, free thyroxine and free triiodothyronine were measured. His FSH, LH, ACTH, cortisol, prolactin and testosterone levels were also low.
Magnetic resonance imaging and computed tomography scan showed a normal-sized pituitary gland entirely embedded in a dense, oedematous, contrast-enhancing mass, and a total destruction of the nasal septum with the absence of conchae and severely impaired sinus walls. A transnasal biopsy showed an acute necrotising, non-specific and non-granulomatous inflammation. Although cocaine-induced panhypopituitarism was suspected, Wegener's granulomatosis could not be excluded. Serology on ANCA showed a strongly positive C-ANCA titre (320 U/l) with specificity for HNE. A cocaine-induced HNE-ANCA-associated panhypopituitarism was diagnosed.
Our patient was advised to quit using cocaine immediately and was initially treated with glucocorticoids and testosterone, followed by thyroxine. This led to a dramatic clinical response with an increase of appetite, weight gain and regained energy. After 2 years, the patient is well and his ANCA titre is no longer positive.
Conclusion: We describe the first documented case of cocaine-induced panhypopituitarism associated with HNE-specific ANCA.
Introduction
Chronic intranasal use of cocaine (‘snorting’) can cause severe local damage to the nasal septum, sinuses and palate, the so-called cocaine-induced midline destructive lesions (CIMDL) (1). Use of cocaine is also associated with the presence of anti-neutrophil cytoplasmic antibodies (ANCA) (2).
The combination of CIMDL and a positive ANCA titre can mimic vasculitides like Wegener's granulomatosis (WG) with resultant diagnostic and therapeutic dilemmas. The pituitary gland is anatomically in close relation with the nasal cavity and therefore could, theoretically, be involved in cocaine-induced processes.
We report a cocaine-abusing patient presenting with a panhypopituitarism, accompanied by CIMDL and human neutrophil elastase (HNE)-specific ANCA.
Case
A 41-year-old man presented to our outpatient clinic with extreme progressive fatigue, which had left him bedridden over the previous 4 weeks. He also mentioned loss of appetite with a weight loss of 20 kg since the onset of his fatigue 6 months before. Concomitant complaints were general skeletal and muscular pains, brittle nails and impotence. His medical history was unremarkable and no use of prescription medication was mentioned, although he admitted snorting cocaine twice a week over the previous 6 years.
Physical examination showed a very pale and skinny man. His weight was 67 kg (body mass index=22) and he looked emaciated. His blood pressure was 110/75 without signs of orthostatic hypotension. Laboratory results (Table 1) showed normal renal and liver function, but did reveal iron deficiency anaemia.
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Since these biopsy results could not prove nor exclude WG, serology on ANCA was done. A positive C-ANCA titre was found (1:160) with specificity for proteinase 3 (PR3 antibodies 152 U/l). These results raised suspicion of WG. However, Wiesner et al. (2) found elevated ANCA titres with specificity for HNE in 84% of cocaine users suffering CIMDL, while no HNE-ANCA were detected in patients with WG. With this in mind, additional testing on HNE-ANCA was performed, and indeed a HNE-ANCA was found, not a PR3-ANCA.
We made a diagnosis of a cocaine-induced panhypopituitarism with CIMDL and HNE-ANCA.
Our patient was strongly advised to quit using cocaine immediately and was initially treated with glucocorticoids and testosterone, followed by thyroxine. This led to a dramatic clinical response with regained energy, increase of appetite and weight gain. After 2 years, the patient is well, but still uses hormone replacement therapy as the pituitary function has not improved. Follow-up MRI shows severe destruction of the nasal cavity and a normal-sized pituitary gland surrounded by contrast-enhancing mass with less oedema than at the diagnosis (Fig. 2). He has still abstained from using cocaine and ANCA titres are repeatedly negative.
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We describe a man with a history of intranasal cocaine abuse with a panhypopituitarism and a largely destroyed nasal cavity accompanied by the presence of HNE-specific ANCA.
Cocaine use can mimic the nasal abnormalities and serology results found in autoimmune vasculitides, such as WG, which is characterised by granulomatous inflammation in the upper and lower airways, vasculitis and necrotising glomerulonephritis (3).
ANCA are antibodies targeting neutrophil antigens such as PR3, myeloperoxidase (MPO) or HNE, and are associated with several vasculitides (4).
Ninety percent of WG patients have positive ANCA titres, of which 80% are PR3 specific, while the remainder has MPO-specific ANCA. By contrast, HNE-specific ANCA are found in 84% of CIMDL patients and are solely associated with intranasal cocaine use, not with autoimmune vasculitis (2). Therefore, the specificity of ANCA (either PR3 or HNE) enabled us to discriminate between a cocaine-induced process mimicking a WG limited to the upper airways and a true limited WG, as treatment differs widely between these two diagnoses.
In retrospect, in our patient HNE-specific ANCA was found instead of PR3-specific ANCA. The initially found PR3-ANCA was probably a false positive due to cross reaction between PR3 and HNE, as both encoding genes are closely clustered on chromosome 19 and have very similar transcriptional properties and function (5).
The combination of indirect immunofluorescence, direct ELISA and capture ELISA tests maximises the sensitivity for HNE-ANCA testing (2) and only then is differentiation possible between a true vasculitis and cocaine-induced, ANCA-associated inflammatory process.
The combination of HNE-specific ANCA and biopsy-proven, non-granulomatous, necrotising inflammation ruled out limited WG in our patient.
Furthermore, a S. aureus culture was grown from the biopsy of our patient's nasal cavity, a colonisation seen in almost every intranasal cocaine abuser (6), but also found three times more often in WG patients than healthy individuals (7).
S. aureus produces a so-called super-antigen that not only provokes an immune response but also possibly induces an autoimmune response by the production of ANCA by B cells (8). However, a specific target antigen in S. aureus induced ANCA has not been described. In our patient, ANCA titres dropped dramatically after quitting cocaine abuse even though successful eradication of S. aureus was not yet accomplished. Therefore, in this case, S. aureus is not thought to be the inducing factor for ANCA production.
Hypopituitarism can result from insufficient production of hypothalamic hormones or by the inability of the pituitary gland itself to produce hormones due to brain damage, tumours, infection or infarction (9, 10). Our patient did not report any head trauma or skull radiation and did not have any cardiovascular risk factors. Therefore, in our patient, our initial differential diagnosis consisted of cocaine-induced hypopitiutarism, WG, empty sella syndrome or hypophysitis as possible causes for his panhypopituitarism. Insel et al. (11) described a case of cocaine-induced pituitary infarction leading to hypopituitarism, diabetes insipidus and paralysis of cranial nerve VI. However, ANCA could not be detected. By contrast, in our patient, no signs of pituitary infarction leading to radiographic signal inhomogeneity were seen. CT and MRI showed severe damage to the nasal cavity and its walls and revealed a pituitary gland embedded in an oedematous, contrast-enhancing and therefore possibly inflammatory mass. Tumour or hypothalamic abnormalities were not seen. Continuation of the gadolinium contrast from the sella turcica to the sphenoidal and maxillary sinuses raised the suspicion of intranasal cocaine infiltrating through an apparently impaired sphenoid bone and therefore, theoretically, causing local damage to the pituitary gland.
Our patient's condition improved dramatically after treatment with corticosteroids, testosterone and thyroxine. We also proposed GH substitution but the patient refused this therapy as he did not expect any further improvement of his quality of life. Although a few studies have demonstrated some beneficial effects of GH substitution on the quality of life in patients with hypopituitarism, this is still a matter of debate (12, 13).
Biopsy of the area surrounding the pituitary gland showed a non-specific inflammation, and although direct biopsy of the pituitary gland could not be obtained, the combination of the patient's history, clinical findings, radiology, serology, biopsy and the drop of ANCA titre after ceasing cocaine use led us to the first documented diagnosis of cocaine-induced, HNE-ANCA-associated panhypopituitarism.
In conclusion, our message is: i) To be aware of the possibility of panhypopituitarism in cocaine abusers and ii) to be informed of a possible false positive PR3-ANCA instead of HNE-ANCA due to cross reaction.
Declaration of interest
There is no conflict of interest that could be perceived as prejudicing the impartiality of the scientific work reported.
Funding
This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
References
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