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Orthostatism, Constipation, and Early Satiety

A 65-year-old woman with a history of Graves disease, status post radioactive iodine therapy, and a biopsy-proven benign calcified breast nodule sought care for evaluation of multiple symptoms. She had constipation for 8 years, with prior fecal urgency, and intermittent diarrhea for the previous year. She was diagnosed with irritable bowel syndrome. Her weight remained stable until 1 1/2 years earlier, and she had lost 6.8 kg. For the previous 3 years, the patient had experienced multiple urinary symptoms including hesitancy, urgency, incontinence, and retention. She was diagnosed with a cystocele, the correction of which did not help. She had noted difficulty focusing her eyes when moving from a dark to a well-lit environment, or vice versa. She also reported orthostatic light-headedness for 1½years, which worsened on exposure to a hot environment. Neurologic examination showed abnormally dilated pupils with prominently sluggish constriction in response to light. Autonomic reflex screening indicated patchy postganglionic sympathetic sudomotor, marked cardiovagal, and cardiovascular adrenergic failure, with neurogenic orthostatic hypotension. Thermoregulatory sweat testing showed 82% anhidrosis. A nuclear medicine gastric-emptying study indicated delayed gastric emptying and colonic hypomotility. Serum testing was markedly positive for ganglionic (alpha 3) acetylcholine receptor autoantibodies. The patient was diagnosed with autoimmune autonomic ganglionopathy. The patient received intravenous immunoglobulin. She returned and reported 80% improvement in all symptoms, and neurologic examination showed normal pupillary response to light. Autonomic reflex screening indicated improvement of her adrenergic function, and thermoregulatory sweat testing showed an impressive improvement of her sudomotor function. Her postganglionic sympathetic sudomotor and cardiovagal function remained impaired. Gastric emptying remained mildly delayed. She was maintained on intravenous immunoglobulin, which was later tapered after azathioprine was started. Autoimmune autonomic ganglionopathy usually presents subacutely, much like other autoimmune neurologic diseases. Typical features of this disorder are the impaired pupillary reaction to light and prominent sicca symptoms, indicating prominent cranial parasympathetic (cholinergic) impairment. Also consistent with this diagnosis are the prominent gastrointestinal tract symptoms. Prominent cholinergic failure helps distinguish autoimmune autonomic ganglionopathy from peripheral autonomic neuropathy or neurodegenerative disorders such as pure autonomic failure.