Autoimmune hypophysitis (AH) is a rare autoimmune disease that occurs when the pituitary gland is infiltrated with lymphocytes and plasma cells, leading to impaired hormonal secretion. Rare cases of association of systemic lupus erythe-matosus (SLE) with AH have been reported in literature but mainly in adult population. AH commonly involves anterior pituitary; labelled as lymphocytic adenohypophysitis (LAH) but it can also involve posterior pituitary which is called lymphocytic infundibulo-neurohypophysitis (LINH) [1-4]. Herein, we report a rare case of lupus in a male child who presented with features of central hypothyroidism and diabetes insipidus that was diagnosed as SLE-associated AH. He was treated with pulse methylpre-dnisolone and cyclophosphamide with hormone replacement.

A 14-year-old male child, fourth issue of a non-consanguineous marriage was admitted with history of fever, weight loss, pallor and generalized weakness since one month. There was no history of rash, bleeding manifestations, abdominal distension, night sweats, oral ulcers, icterus, headaches, visual disturbances or joint swelling. He had received multiple oral antibiotics with no improvement. In the past, he had suffered a stroke at ten years of age with MRI brain showing acute lacunar infarct in right corona radiata. Birth history was uneventful and he was immunized as per schedule. Anthropometric parameters and vitals, including blood pressure, were normal. Clinical examination revealed malar rash, oral ulcers, severe pallor with moderate hepato-splenomegaly. Laboratory investigations revealed anemia (Hb, 6.4 g/dL), direct Coombs test (DCT) positive, normal white blood cell (WBC) counts (WBC, 7.9×109/L, Neutrophils 49%, Lymphocyctes 51%), thrombocytopenia (Platelet count, 30,000/cmm), raised ESR (81 mm at end of one hour), prolonged activated partial thromboplastin time (APTT) [Test, 54 sec (26.9-36.3)], high spot urine protein creatinine ratio (0.9, normal <0.2) with normal liver enzymes, serum electrolytes and X-Ray chest. Immunological investigations showed strongly positive anti-nuclear antibody (ANA titres 1:2560, speckled pattern), low serum complement C3 (C3-60 mg/dL; normal range 82-173 mg/dL) and C4 (C4 11.2 mg/dL; normal range: 13-46 mg/dL), positive anti-cardiolipin IgM antibody, beta-2 glycoprotein IgM antibody and lupus anti-coagulant. Anti-double stranded DNA antibody and anti-Smith (anti-Sm) antibody were negative. Ophthalmology examination showed retinal hemorrhages. Thyroid function test revealed central hypothyroidism [low free T3 (<1 pg/mL), low free T4 (0.46 ng/dL), and low TSH (<0.01uIU/mL)], with positive anti-thyroid peroxidase (anti-TPO) antibodies. During the hospital stay, child started developing delirium and agitation along with polyuria. Serum osmolality was high (320 mOsm/kg). Magnetic resonance imaging (MRI) showed absence of posterior pituitary bright spot in T1-weighted imaging consistent with diabetes insipidus. Serum cortisol, prolactin, and sex hormone levels were within normal limit. Parents did not consent for renal biopsy. Although desirable, IgG4-related disease (IgG4-RD) workup could not be done due to financial constraints.　A diagnosis of SLE with multiple organ involvement with AH was made. He was initiated on intravenous pulse methylprednisolone and cyclophosphamide followed by oral steroids, monthly cyclophosphamide, hydroxychloroquine, warfarin, thyroid replacement and oral desmopressin, with a close follow up.

In our patient, SLE was diagnosed based on constitutional symptoms, malar rash, oral ulcers, thrombocytopenia with auto-immune hemolytic anemia (Evans syndrome), low WBC counts, high ESR, ANA positivity, low complement levels, positive antiphospholipid antibody, and high urine protein creatinine ratio. AH is a rare disease, mainly affecting females though in our case it was a male. It has incidence reported to be 1 in 9 million [5] but the actual number may be more, particularly as IgG4-RD and involvement of the hypophysis by systemic pathologies has increasingly been recognised [6]. AH can be primary (idiopathic) or secondary to sella and parasella lesions, systemic diseases, or drugs (mainly immune checkpoint inhibitors). The predominant feature of LINH is central diabetes insipidus which was present in our patient. The diagnosis of AH was made when our patient showed features of central hypothyroidism and diabetes insipidus with loss of normal posterior pituitary bright spot on T1-weighted MRI. The gold standard of diagnosis is pituitary biopsy which reveals massive infiltration of lymphocytes and plasma cells in the pituitary gland but is usually denied by patients due to its invasive nature. Our patient is similar to the case reported by Jing, et al. [4] in which a 15 year lupus child revealed low levels of sex hormones, thyroid hormones and serum cortisol with MRI of pituitary region demonstrating an enlargement of the pituitary stalk. She was diagnosed as LINH associated with SLE and responded well to glucocorticoids and cyclophosphamide [4]. We treated our patient with steroids, cyclophosphamide, hydroxy-chloro-quine, hormone replacement and warfarin with significant clinical improvement in constitutional symptoms, normali-zation of acute phase reactants, complement levels, thyroid function and urine proteinuria at 3 months of follow up. Warfarin was added to treatment protocol considering positive antiphospholipid antibody and history of prior lacunar infarct. To the best of our knowledge this is the first case reported from India with features of AH in a case of juvenile SLE.

Our case demonstrates association of SLE and AH in children. In the presence of central hypothyroidism and diabetes insipidus in a lupus patient, endocrine hormonal evaluation and an MRI of pituitary gland is warranted to rule out AH.

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