POEMS syndrome is a rare multisystem disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. We report the first case of spontaneous recovery of adrenal insufficiency in a patient with POEMS syndrome treated with autologous hematopoietic cell transplantation. We conclude that in patients with POEMS syndrome, adrenal insufficiency should be regularly assessed for potential recovery.
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a rare disorder, which is considered to be an osteosclerotic variant of myeloma. We describe the first report of the spontaneous recovery of adrenal insufficiency in a patient with POEMS syndrome treated with autologous hematopoietic cell transplantation.
A 42-year-old woman was referred to the endocrine clinic with a 5-month history of tiredness, constipation, and amenorrhea. Clinical examination revealed the following: blood pressure, 100/60 mm Hg; increased skin pigmentation; bilateral axillary lymphadenopathy; and hepatosplenomegaly. Initial investigations revealed primary hypothyroidism (high thyroid-stimulating hormone [TSH] and low free thyroxine [fT4]). An adrenocorticotropic hormone (ACTH) stimulation test confirmed cortisol insufficiency with a peak cortisol level of 341 nmol/L (> 550 nmol/L).
She was treated with thyroxine and hydrocortisone, and underwent further investigations for lymphadenopathy and hepatosplenomegaly. Liver biopsy showed nonspecific inflammatory changes, and trephine bone marrow biopsy demonstrated findings suggestive of an underlying myeloproliferative process with no features of lymphoma or leukemia. Bone marrow cytogenetics was normal. Several months later, despite initial improvement in symptoms, the patient deteriorated and developed sclerodermatous skin changes and symptoms suggestive of polyneuropathy with predominant motor disability (confirmed on nerve conduction studies). At this stage, POEMS syndrome was suspected; on further investigations, free immunoglobulin (Ig)A-lambda light chains were detected in the urine specimen, and bone scan revealed an osteosclerotic focus in the left pelvis. These features were diagnostic of POEMS syndrome. She was treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation, which led to a dramatic response. Four years later, she exhibited cushingoid features, with weight gain, facial plethora, and central obesity. Iatrogenic Cushing's syndrome was suspected, and hydrocortisone dose weaned off gradually over 2 months. An ACTH stimulation test was subsequently performed, which revealed normal adrenal function with a peak cortisol level of 641 nmol/L. Three months later at follow-up, she was asymptomatic, on no steroid replacement, with a normal 9:00 AM cortisol level of 520 nmol/L (280-700 nmol/L).
The diagnosis of POEMS syndrome is based on the presence of 2 major criteria (monoclonal plasma cell proliferative disorder and polyneuropathy) and at least 1 minor criterion, such as endocrinopathy, organomegaly, sclerotic bone lesions, skin changes, papilledema, Castleman's disease, and edema.
Endocrinopathy, found in nearly 69% of patients, is a central feature of POEMS syndrome. Many endocrine disorders have been described, including hypogonadism (79%), hypoadrenalism (67%), hypothyroidism (58%), glucose intolerance (48%), hyperprolactinaemia (29%), and hypocalcemia (27%). The pathogenesis of the endocrinopathies in POEMS syndrome remains unclear. The presence of normal endocrine glands at autopsy and the absence of circulating antibodies directed against specific hormone receptors suggest that the endocrine gland dysfunction in this syndrome is likely to be functional, rather than due to structural damage to the endocrine glands. Spontaneous recovery of an endocrine dysfunction in POEMS syndrome has not been described in previous studies. To our knowledge this is the first reported case of spontaneous clinical and biochemical recovery of adrenal insufficiency in a patient with POEMS syndrome. In view of the potential for adrenal function recovery in POEMS syndrome, and in order to avoid unnecessary and harmful exposure to long-term glucocorticoid therapy, we recommend regular reassessment of adrenal function in this condition.
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Medscape J Med. 2009;11(1):21 © 2009
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