ODP057 The Unusual Case of Hypercortisolism in a Patient with Juvenile Onset Hypophosphatasia

Abstract

Abstract Juvenile onset hypophosphatasia is a rare, genetic disease that is caused by inactivating mutations in the ALPL gene which encodes tissue non-specific alkaline phosphatase (TNSALP). This leads to decreased activity of the TNSALP enzyme in target tissues and accumulation of TNSALP substrates, including inorganic pyrophosphate, an inhibitor of mineralization. This disease is characterized by low levels of alkaline phosphatase in serum and bone, osteomalacia, and periodontal disease. Patients with juvenile onset hypophosphatasia present with premature loss of primary teeth, delayed walking, and a waddling gait. These symptoms may improve spontaneously after puberty and recur later in life. Here we report the case of a 51 year old male who presented initially to endocrinology clinic with a metatarsal stress fracture with subsequent diagnosis of osteoporosis, periodontal infections, and associated myopathy and joint calcifications. The patient also had a prior history of a low alkaline phosphatase level as a child. Genetic testing showed a single variant of undetermined significance found in the ALPA gene. Of note, recent lab work for the patient showed AM cortisol 27.7 mcg/dL (reference range 4. 0-22. 0 mcg/dL) with ACTH 60 pg/mL (reference range 6 - 50 pg/mL). Prior 24 hour urine free cortisol measurements with LC/MS have demonstrated elevated values 159 mcg/24 hr and 256 mcg/24 hr (reference range 4. 0 - 50. 0 mcg/24 hr) . However, most recent testing demonstrated 24 hour urine free cortisol 3.6 mcg/24 hr, and the majority of midnight salivary cortisol tests were within normal. Pituitary MRI demonstrated no abnormalities. The patient has in the past reported findings of a dorsocervical fat pad, abdominal striae, and weight gain. There is no history of diabetes mellitus or hypertension, and the patient at this time reports stable weight without current presence of a fat pad or striae. There are no clinical features of Cushing's syndrome on exam. To our knowledge, this is the second case in the literature detailing hypercortisolism in a patient with hypophosphatasia. The etiology of the hypercortisolism is likely multifactorial, with unknown association with hypophosphatasia. Based on the clinical data it appears that the patient's chronic stress, pain, and anxiety are contributing to the hypercortisolism, and that this is not a true Cushing's or cyclical Cushing's case. Repeated midnight salivary cortisol tests have excluded the possibility of Cushing's as well. Presentation: No date and time listed