Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction in the antiphospholipid syndrome: long-term outcome of 16 patients.

CONTEXT: Primary adrenal insufficiency due to bilateral adrenal hemorrhage-adrenal infarction is a rare and life-threatening manifestation of the antiphospholipid syndrome (APLS). Data on the long-term outcome are scarce. OBJECTIVE: The aims of the present study were to analyze the long-term outcome related to APLS per se and to characterize the course of adrenal involvement. DESIGN: We conducted a retrospective study of patients with bilateral adrenal hemorrhage-adrenal infarction secondary to APLS seen in the Department of Internal Medicine of Pitié-Salpêtrière Hospital in Paris (France) between January 1990 and July 2010. RESULTS: Three patients died during the acute phase related to APLS manifestations. Sixteen patients (7 males; 9 females) were followed up during a median period of 3.5 years (range 0.3-28.1 years). Three episodes of recurrent thrombosis were noted. One patient died from cerebral hemorrhage 3 months after the onset of adrenal insufficiency. Repeated Synacthen tests showed complete absence of response in 8 of the 10 patients assessed; cortisol and aldosterone increased appropriately in one patient and to some extent in another one. Dehydroepiandrosterone levels and 24-hour urinary epinephrine levels remained abnormally low in all evaluated patients. Adrenal imaging performed more than 1 year after the initial event revealed completely atrophic glands in 9 of 11 patients. CONCLUSIONS: This particular subset of APLS patients who survive the acute phase has a rather favorable long-term outcome. Although adrenal dysfunction is generally irreversible, adrenocortical function may, at least partially, recover in rare cases. In this view, measurement of early morning cortisol during follow-up is indicated to detect these patients.

Hypophosphatemia related to paraneoplastic Cushing syndrome in prostate cancer: cure after bilateral adrenalectomy.

We report the case of a 71-year-old man with progressive metastatic prostate cancer in whom simultaneous occurrence of paraneoplastic Cushing syndrome (CS) and tumor-induced osteomalacia (TIO) initially was suspected. However, the evolution of biochemical markers of phosphate metabolism during disease course and after bilateral adrenalectomy argued against the diagnosis of TIO. Despite the persistence of progressive prostate cancer, CS and hypophosphatemia resolved in parallel after bilateral adrenalectomy. Thus, these data suggest that paraneoplastic CS per se was involved in the pathogenesis of hypophosphatemia. Calcitriol and intact fibroblast growth factor 23 (FGF23) levels were within the reference range at onset, which is inappropriate in the setting of severe hypophosphatemia. All parameters of phosphate metabolism normalized after resolution of hypercortisolism. Based on the known suppressive effect of glucocorticoids (GCs) on bone remodeling and the inverse relationship between bone turnover rate and circulating FGF23 levels, we postulate that GCs interfere indirectly with phosphate homeostasis by inducing inappropriate FGF23 production and release. This mechanism could further aggravate the hypophosphatemia resulting from GC-induced inhibition of intestinal phosphate absorption. Studies directed at the identification of the molecular pathways in bone mediating the interference of GCs with phosphate metabolism are warranted.

Fibroblast growth factor 23 and its role in phosphate homeostasis.

Phosphate homeostasis is complex and incompletely understood. The identification of different factors involved in the regulation of phosphate balance, also called phosphatonins, has largely changed our view on the regulation of phosphate homeostasis. The active role of bone has been demonstrated clearly. Currently, maintaining phosphate homeostasis is considered the result of a complex network of endocrine feedback loops between parathyroid gland, kidney, and bone. This review describes current knowledge on fibroblast growth factor 23, which is one of the best studied phosphatonins.