Pulmonary Langerhans cell histiocytosis (LCH) is a rare interstitial lung disease in adults that is a part of diseases caused by infiltration of Langerhans cell across multiple organs, such as the lungs, bones, skin, pituitary gland, and lymph nodes. Among cases of multi-system LCH, simultaneous invasion of the lung and the pituitary gland is uncommon. Adult patients with pulmonary LCH may also develop extrapulmonary involvement in 17% of cases, such as diabetes insipidus in 5%-7% of patients. Over 90% of LCH cases occurs in smokers, and the disease typically improves following smoking cessation. Herein, we report a rare case of pulmonary LCH presenting with central diabetes insipidus and type 2 diabetes mellitus at diagnosis and improved after 1 year of smoking cessation.

Case Report

A 42-year-old male was referred from a local clinic with a 1-year history of polydipsia and polyuria. He also complained of dry cough and dyspnea for 1 month. He was a current smoker with a 20 pack-year history and had been diagnosed with hypertension 4 years prior. The family history was unremarkable. On admission, the blood pressure was 147/81 mm Hg, heart rate was 120 per minute, respiratory rate was 16 per minute, and body temperature was 36.8℃. His height was 162 cm and the body weight was 82 kg (body mass index, 31.2). He appeared to be chronically ill. He did not present with pale conjunctiva, cyanosis, or clubbed fingers. Physical examination of the chest revealed fine crackle of both upper lung fields, and there was no audible cardiac murmur. The patient had no skin rash or palpable lymph nodes. The rest of the exam was unremarkable.

Complete blood count revealed a total leukocyte count 11,480/mm3 (neutrophil, 61.1%; lymphocyte, 28.1%; monocyte, 7.0%; eosinophil, 1.2%; basophil, 0.3%), hemoglobin 14.2 g/dL, hematocrit 42.1%, and platelet count 421,000/mm3. Serum chemistry demonstrated a total protein level of 7.1 g/dL, albumin 4.6 g/dL, blood urea nitrogen 5.5 mg/dL, creatinine 0.83 mg/dL, aspartate transaminase 37 U/L, alanine transaminase 47 U/L, total bilirubin 0.34 mg/dL, and C-reactive protein 0.62 mg/dL.

The patient was also underwent an endocrinologic evaluation of the anterior and posterior pituitary including the following: thyroid stimulating hormone, 1.146 µIU/mL (0.35-5.50 µIU/mL); total T3, 1.40 ng/mL (0.60-1.81 ng/mL); free T4, 1.45 ng/dL (0.83-1.76 ng/dL); growth hormone, 0.102 ng/mL (<13.0 ng/mL); insulin-like growth factor-1, 182.0 ng/mL (101-267 ng/mL); prolactin, 4.98 ng/mL (2.1-17.7 ng/mL); lutenizing hormone, 5.23 mIU/mL (1.5-9.3 mIU/mL); follicular stimulating hormone, 9.69 mIU/mL (1.4-18.1 mIU/mL); testosterone, 3.53 ng/mL (2.8-11.0 ng/mL); cortisol, 25.14 µg/dL (4.3-22.4 µg/dL); adrenocorticotrophic hormone, 54.6 pg/mL (12.0-60.0 pg/mL); and antidiuretic hormone, 4.23 pg/mL (<6.7 pg/mL). Osmolality of the urine was 87 mmol/kg and serum osmolality was 280 mmol/kg. Urine specific gravity was 1.001 (1.015-1.030). Water deprivation test and a vasopressin response trial revealed a diagnosis of diabetes insipidus ( Table 1 ). For evaluating whether the cause of central diabetes insipidus was autoimmunity, IgG4 subclass antibody was measured and its level revealed 208.0 mg/L (30-2,010 mg/L). Fasting plasma glucose was 145 mg/dL and hemoglobin A1c was 7.0%.

Magnetic resonance imaging of the hypothalamic-pituitary system revealed neither infundibular enlargement nor space occupying lesions of the pituitary or hypothalamic glands. But, the hyperintense signal of the posterior pituitary on T1-weighted images was not detectable which is typically absent in LCH patients with central diabetes mellitus ( Figure 1 ).

Chest radiograph was notable for reticular opacities in bilateral upper and middle lung fields. On computed tomography of the chest, numerous irregularly shaped cysts and centrilobular nodules were observed in the bilateral lung fields. These findings were more prominent in the upper lobes but were not visible on both costophrenic angles ( Figure 2A ).

The patient underwent bronchoalveolar lavage, and the lavage specimen was analyzed for further evaluated. The leukocyte count of the lavage was 342/µL, and the differential count was reported as lymphocyte 17%, polymorphic neutrophil 4%, basophil 2%, and monocyte 1%. Acid-fast bacilli staining and culture of the sputum, fungus culture, and polymerase chain reaction for Mycobacterium tuberculosis were all negative.

On pulmonary function testing, the forced expiratory volume in 1 second (FEV 1 )/forced vital capacity (FVC) ratio was 82%, with an FEV 1 of 3.04 L (93% of predicted value) and FVC of 3.81 L (93% of predicted value). Plethysmography was performed, showing residual volume of 0.68 L (43% of predicted value), and a total lung capacity of 4.49 L (84% of predicted value). Diffusing capacity for carbon monoxide was 15.4 mL/mm Hg/min, which was 60% of the predicted value.

Video-assisted thoracoscopic surgery was performed to obtain a biopsy specimen of the lung in the right upper lobe. On histologic examination, multiple cystic spaces were visible upon a grayish-white granular layer. Immunohistochemical evaluation revealed strong positivity for CD1 and S-100 protein, suggesting diffuse infiltration of the Langerhans cell, confirming the diagnosis of LCH ( Figure 3 ).

Involvement of additional systems was evaluated using radiographic examination. A skeletal survey including skull, vertebral, and pelvic series revealed no abnormality. Abdominal computed tomography scan revealed no hepatic or splenic abnormalities. A positron emission tomography-computed tomography was performed to identify lesions potentially missed by other modalities but did not reveal further systemic involvement.