A rare case of cranial diabetes insipidus in a patient with orbital xanthogranulomatous disease
HL Yap1, F Wernig1, C Limback-Stanic2, N Martin1, R Kaushal3
1 Department of Endocrinology, Charing Cross Hospital, Imperial College Healthcare NHSTrust, London, UK
2 Department of Cellular Pathology, Charing Cross Hospital, Imperial College Healthcare NHSTrust, London, UK
3 Department of Endocrinology, West Middlesex University Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, Middlesex, UK
Case Study: This 46 year old gentleman came to the attention of the endocrine team when his astute GP asked for advice on further investigations into his symptoms of polydipsia and polyuria. The patient had had these symptoms for 3 months and had not presented earlier as the country was in the middle of COVID lockdown, and the patient was shielding. He complained of feeling thirsty all the time and was drinking in excess of 22 pints of fluid daily. He was frequently passing large volumes of urine and estimated passing at least 3 to 4 litres of urine daily.
His past medical history was relevant for peri-orbital xanthogranulomatous disease, which was first diagnosed in 2007 and previously debulked with bilateral orbital decompression in 2011. He developed proptosis of his right eye in 2011 and had initially failed to respond to Methotrexate, 6-Mercaptopurine or Ciclosporin. He was then started on Tacrolimus with good response, however his disease relapsed when weaning of Tacrolimus was attempted. He had further extension of his periorbital disease (predominantly the left eye), enlargement of his left submandibular gland and left nasal septal deviation in 2017. He was subsequently listed for a left lid, lacrimal duct and orbital decompression, as well as excision of his left submandibular gland lymph node in 2018/2019. Interestingly, histology from the left lacrimal gland showed a lymphocytic infiltrate with no particular features of granulomatous change or IgG4 disease, but histology from the left submandibular gland showed chronic sclerosing sialadenitis, with total IgG4-positive plasma cells of 82/hpf and an IgG4:IgG ratio of 200%, consistent with IgG4 related disease. Apart from Tacrolimus, he was also taking a steroid inhaler for asthma and a steroid nasal spray. He had a family history of diabetes mellitus; his father had type 2 diabetes and was previously on dialysis (now deceased), and his sibling had type 1 diabetes.
Investigations: Initial investigations excluded diabetes mellitus as a cause for his symptoms, HbA1c was 40 mmol/mol and fasting plasma glucose was 6.3 mmol/L. His sodium level was 139 mmol/L, creatinine 83 umol/L and eGFR >90 ml/min/1.73m2. His pituitary profile showed normal thyroid function, prolactin, growth hormone and IGF-1 levels. Short SynACTHen test had a normal response, with baseline cortisol of 301 nmol/L, rising to 631 nmol/L at 30 minutes and a normal ACTH level of 19.8 ng/L. However, he had secondary hypogonadism with a low testosterone level of 1.2 nmol/L (normal SHBG of 28.8 nmol/L), low normal FSH levels of 2.4 u/L and low LH levels of 1.3 u/L. He denied erectile dysfunction or other symptoms of hypogonadism. A water deprivation test was carried out and this confirmed cranial diabetes insipidus, with dehydration causing excessively concentrated plasma above 300 mOsmol/kg alongside inappropriately hypotonic urine, and DDAVP administration resulting in concentrated urine to above 150% of previous highest level. He was started on Desmopressin DDAVP and testosterone replacement.
He went on to have a pituitary MRI which was discussed at the Imperial Pituitary multidisciplinary team (MDT) meeting. It was felt that there was mainly inflammatory tissue with posterior stalk thickening, rather than a pituitary adenoma. There was also paranasal sinuses involvement but no dural thickening.
Discussion: The working diagnosis includes an inflammatory IgG4-mediated process infiltrating the pituitary gland, resulting in cranial diabetes insipidus and secondary hypogonadism. This patientís hypophysitis is likely to be related to his peri-orbital xanthogranulomatous disease, which is thought to be a rare non-Langerhans histiocytosis1. Peri-orbital xanthogranulomatous disease has recently been found to be associated with systemic IgG4-related disease1. The often chronic and relapsing nature of IgG4-related disease commonly requires immunosuppressive treatment with steroids and steroid-sparing agents such as Rituximab to maintain long-term remission2, 3. We have organised a further MDT meeting between the endocrine, dermatology, vasculitis, radiology and histopathology specialties to discuss this gentlemanís further management/treatment, especially since he has previously failed to respond to other immunosuppressants.
1. Burris CKH, Rodriguez ME, Raven ML, Burkat CN, Albert DM. Adult-onset asthma and periocular xanthogranulomas associated with systemic IgG4-related disease. Am J Ophthalmol Case Rep. 2016; 1: 34-37.
2. Boharoon H, Tomlinson J, Limback-Stanic C, Gontsorova A, Martin N, Hatfield E, et al. A case series of patients with isolated IgG4-related hypophysitis treated with Rituximab. J Endocr Soc. 2020; 4(6): 1-9.
3. Smith C, Hameed S, Rose GE, Wernig F. A 61 year old man with pancreatitis, pituitary dysfunction, and painful exophthalmos. BMJ. 2019; 364: I93.