Symmetrical craniofacial hypertrophy in patients with tertiary hyperparathyroidism and high‐dose cinacalcet exposure

Abstract

We are reporting on a series of two patients with end-stage renal disease on hemodialysis, presented for surgical parathyroidectomy secondary refractory hyperparathyroidism. Both patients had failed maximized medical managements, including higher-than-usual doses of the calcimimetic cinacalcet (270 and 180 mg/day, respectively). On physical exam, both patients had marked symmetrical craniofacial hypertrophy with coarse distortion of facial features, similar in appearance to past reports of Sagliker syndrome. On X-ray and computed tomographic exam, they had peculiar areas of bone absorption on the skull, imitating the radiologic appearance of multiple myeloma. Bone biopsy of the maxilla, however, did not show the expected brown tumor, but rather described only fibrosis and reactive bone formations. This phenotype developed while being on cinacalcet, progressed despite escalation of therapy, and improved only after parathyroidectomy. Both patients developed massive "hungry bone syndrome" after parathyroidectomy necessitating prolonged i.v. calcium infusion. This pattern of severe facial distortion likely represented an adverse consequence of severe tertiary hyperparathyroidism, along with supraphysiologic dose of cinacalcet administration and 25-hydroxy vitamin D deficiency in sensitive individuals. The genetic base of this observation remained unexplained.

Targeted surgical parathyroidectomy in end‐stage renal disease patients and long‐term metabolic control: A single‐center experience in the current era

“…In our cohort, the degree of ALP elevation seems to correlate best with post‐PTX hypocalcemia and LOS. Looking at this phenomenon from a different angle, a massive elevation of ALP is a potential give‐away for an elevated osteoblast mass and a precipitous drop in calcium after surgery . Bone‐specific ALP is an even better predictor of the expected bone morphology .…”

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism

“…A cohort of 62 consecutive persons with RHPT admitted for PTx identified a rate of 27.4% of them with HBS which correlated with younger age, increased body weight, elevated AP, and low serum calcium (as independent parameters), but did not find any association between iPTH values, neither the use of drugs such as cinacalcet or paricalcitol before PTx and HBS [110]. However, cinalcet might be found in the records of patients with chronic kidney disease before they were referred for PTx (and developed HBS), this aspect mostly indicating either an attempt to medically control the associated PT condition without PTx or a severe form of RHPT that became no responsive to medical therapy [111].…”

“…Despite a generous level of statistical evidence in RHPT according to the mentioned studies, since the topic of HBS is sometimes a matter of individual decision, we analyzed the published case reports, and identified another 25 papers with post-operatory HBS (7 cases series that enrolled 2 to 10 patients per series, and 18 single case reports, a total of 48 patients with RHPT-related HBS, aged between 23 and 74 years (these articles were published between 1989 and 2022) [8,25,26,31,111,[119][120][121][122]136,137,141,[143][144][145][146][147][148][149][150][151][152][153][154][155] (Table 6). Table 6.…”

Brown tumor of the thoracic spine presenting with paraplegia in a patient with peritoneal dialysis

“…However, our case was under both calcitriol and cinacalcet treatment for 4 years and iPTH levels were not controlled well by medical treatment option. Otherwise, craniofacial hypertrophy has been reported in a patient with tHPT under high-dose cinacalcet treatment [13]. The effect of cinacalcet in bone formation remains to be elucidated in severe HPT cases.…”