Cushing disease and hypophosphatasia are rare conditions that may be both responsible of an important impairment of bone metabolism with increased fracture risk. We reported for the first time a case of a 43-year-old woman that came at our attention for recent onset of alopecia and amenorrhea. At the anamnesis, she denied any past relevant events and no drug assumption. At the physical examination, she presented rubeosis and facies lunaris and central adipose distribution (waist circumference 130 cm). The preliminary laboratory tests showed increased free urinary cortisol in two subsequent measurements, high ACTH values and normal blood cortisol level. Furthermore, the 1 mg dexamethasone test was performed showing a lack suppression of cortisol (cortisol post-dexamethasone: 289 mmol/l) suggestive for hypercortisolism. Suspecting a Cushings disease, a desmopressin test was done showing ACTH and cortisol response compatible with pituitary genesis of hypercortisolism. The pituitary MRI confirmed the presence of a suprasellar macroadenoma. Therefore the patient underwent transnasalsphenoid pituitary adenomectomy obtaining disease remission. The histological examination showed a papillary-like neoplasm with weakly and diffusely anti-ACTH antibody positive cells with Ki67 equal to 1%. In the screening evaluation of the patient, a bone densitometry was also performed showing no relevant abnormalities. In the mean time, the father of the patient was under our evaluation for multiple bone fractures resulting from low traumas. All secondary causes of osteoporosis were ruled out and hypophosphatasia was suspected based on high vitamin B6 levels (124 nmol/l with normal value: 1955 nmol/l). The genetic analysis detected a germline mutation c1366G>A (p.Gly456Arg) in heterozygosity at the exon 12 of the alkaline phosphatase gene (ALPL), compatible with hypophosphatasia. Based on the father recent diagnosis, we tested total and bone alkaline phosphatase in our patient resulting low (18 U/l with normal value: 30120 U/l; 3.7 microgr/l with normal value: 4.727 microgr/l, respectively) in association with increased vitamin B6 levels (118 nmol/l with normal value: 1955 nmol/l). Although no clinical phenotype suggestive for hypophosphatasia (blue sclera, dental anomalies, hearing or cardiological problems, hystory of previous fractures) was present, the patient underwent to blood test examination for the genetical analysis showing the same fathers mutation.
Conclusion: To our knowledge, this the first case of patient with Cushing Disease and Hypophosphatasia in absence of bone abnormalities. The clinical and radiological evolution of this phenotype is unclear and need periodical examination to detect possible future complications.
18 - 21 May 2019
European Society of Endocrinology