An interesting case of autoimmune hypopituitarism associated with myaesthenia

AM Gharib Ahmed1, R Andrews, Musgrove Park hospital, Taunton and Somerset Foundation Trust

A 46 year old man, previously well and healthy until he presented with vague symptoms of extreme fatigue, arm and leg weakness, loss of libido, anorexia, double vision and nocturia. He was initially referred to the neurologists owing to the limb weakness and diplopia. Few weeks later, he was referred to the endocrine team with fatigue and polyuria. Initial physical and biochemical assessment confirmed that he had pan-hypopituitarism (Glucocorticoid, Gonadotropins, Thyrotropin and ADH axes dysfunction) with no visual field deficits, headache, compressive symptoms, olfactory problems or a relevant family history. He presented in March during the lockdown, so he was admitted in a COVID19-free ward under endocrine-neurology co-management to expedite the investigations and start high dose prednisolone to control the myasthenic symptoms.

Hormonal workup: FBC and routine biochemistry are all normal, sodium is 141 mmol/L, 9 am cortisol 13 nmol/L,  FSH and LH are1.4 and 0.5 u/L, Testosterone <0.5 nmol/L, TSH 0.2 mu/L, Free T4 4.2 pmol/L, Prolactin <50 miu/L, Plasma Osm 3.5 mOs/KG, Urine Osm 183 mOs/KG (increased to 244 after an overnight fast), IGF-1 10.6 nmol/L and  IGFBP-3 4.7 mg/dL.

Immunological workup: Myasthenia screen is positive for AChR-Abs. TRAB, TPO-Ab are both negative. Full autoimmune and paraneoplastic screen is negative. Anti-GAD Abs is strongly positive.  Serum IgG4 levels are normal.

Imaging: MRI head revealed a normal study apart from loss of the normal posterior pituitary high signal.  CT Chest, abdomen and pelvis showed no evidence of malignancy. There is some fat stranding in the anterior mediastinum that may suggest thymic hyperplasia but no solid evidence of thymoma. NCS/EMG: Findings suggest a neuro-muscular junction disorder and are consistent with myasthenia gravis. He responded very well and was discharged on high dose prednisolone  60 mg OD (to be stepped down gradually till 3-5 mg OD), thyroxine 75-100 mics on alternate days, testosterone isocaproate 250 mg IM monthly , desmopressin 100 mics PO ON and pyridostigmine 300 mg divided over 4 doses daily.

Conclusion: Hypopituitarism is most commonly caused by pituitary-hypothalamic tumors, cysts, vascular events, trauma, infiltrative disorders and radiation. Hypophysitis is a less commonly encountered cause of hypopituitarism. Hypophysitis is either caused by a systemic disease or certain drugs; immune checkpoint inhibitors. Primary hypophysitis can be histologically sub-classified to lymphocytic (autoimmune), granulomatous, xanthomatous, necrotizing and IgG4-related hypophysitis. Autoimmune hypophysitis is usually associated with other autoimmune diseases e.g. Hashimoto thyroiditis, pernicious anemia, myasthenia, rheumatoid arthritis, SLE, Sjogren syndrome, multiple sclerosis and type 1 DM. Hormonal deficiencies could be isolated or combined.

Question for the audience: What is the role of anti-PIT-1 and other novel antibodies in the pathogenesis and diagnosis of lymphocytic (autoimmune hypophysitis)?