Clinical status of Sagliker syndrome: a case report and literature review

Abstract

In a 53-year-old woman, Sagliker syndrome developed during 22 years of treatment with intermittent hemodialysis as a result of severe secondary hyperparathyroidism (SHPT) complicating end-stage renal disease. She failed medical managements and lost her renal graft just after the kidney transplantation due to acute rejection. Although surgical parathyroidectomy was effective, the parathyroid hormone level became extremely high again due to recurrent hyperparathyroidism. It is possible that such patient could survive long-term with dialysis, but prevention of severe SHPT is the most important.

• Chronic renal failure
• hemodialysis
• parathyroid hormone
• Sagliker syndrome
• secondary hyperparathyroidism

Introduction

Sagliker syndrome (SS) is a novel syndrome described in patients with chronic renal failure (CRF) in the course of untreated or inadequately treated secondary hyperparathyroidism (SHPT). It is an exaggerated form of renal osteodystrophy, comprising chronic kidney disease (CKD), SHPT, uglifying appearance to the face, short stature, irregularly scattered skull and facial bone alterations, destruction of maxillary and mandibular bones, irregularly shaped and located teeth, soft and innocent tissue accumulations in the upper oral cavities, class II malocclusion of malocclusion of the upper and lower jaws, upward curved fingertips, knee and scapula deformities, hearing loss and neuropsychiatric disorders.1,2 SS is characterized by marked facial changes resulted from maxillary, mandibularly, dental and nasal bone changes and destructions. In fact, as early as in 1953, Cohen and Diamond had reported that skull alterations in patients with SHPT due to CRF could lead to ugly facial appearance, which was once described as leontiasis ossea,3 bighead4 or swollen face.5 Until 2004, Sagliker defined this clinical status in detail and named it.

The incidence of SS, reported by Sagliker in 2004, was evaluated to be approximately 0.5% in hemodialysis (HD) patients.1 Previously studies have shown the major manifestations of this syndrome, while its therapeutic response and prognosis are rarely mentioned. At present, we would like to show a case of SS in our blood purification center to discuss the clinical status of such patients.

A case report

A 53-year-old Chinese female had been on regular HD program because of polycystic kidney disease in our center since 1991. She used native arteriovenous fistula for dialysis three times a week combined with hemodiafiltration (HDF) once every two weeks. Filter for dialysis was never reutilized due to hepatitis C virus infection in this patient.

Complete residual renal function (RRF) loss occurred in 1996. Increased level of parathyroid hormone (PTH) has been noticed since 1994. Pharmacological medications, such as phosphate binder, active vitamin D were used; however, PTH still remained at the high level (up to 1500 pg/mL). In 1997, she underwent renal transplantation from a dead donor, but due to severe acute rejection, the transplant was removed 10 days after resection. A cadaveric donor kidney retransplantation was done in 2000; however, graft failed once again as a result of super-acute rejection. Since the transplant never took up to a proper function, the patient continued HD treatment. Subtotal parathyroidectomy (sPTX) was performed in 2001 because of the enlarged parathyroid glands and the abnormal PTH level. Total parathyroidectomy (tPTX) with parathyroid auto-graft into the left forearm was done soon afterward as the patient still had high postoperative PTH levels. Before the first PTX, it was about at least 5 years with PTH of >1000 pg/mL, and concentration of PTH decreased to 300 pg/mL after resection. In 2003, forearm auto-grafted parathyroid tissue was partially removed owing to graft-dependent recurrence. During 2004–2012, serum concentration of PTH ranged from 100 pg/mL to 500 pg/mL most of the time, and pharmacological medications of SHPT were always used in the course of dialysis treatment. In 2013, PTH increased again to >1000 pg/mL as a result of relapsing hyperparathyroidism. Operation for the removal of cervical supernumerary glands totally with forearm autotransplant partially was thus done. However, the patient still bore persistently elevated PTH level after resection due to ectopic parathyroid glands in the anterior mediastinum detected by (99 m) Tc-MIBI scintigraphy. The fluctuation of serum PTH level was shown in Figure 1 (data before 1996 unfortunately lost).

Figure 1. The fluctuation of serum parathyroid hormone (PTH) level during 1996–2013. Serum concentration of PTH was 444.35 ± 379.30 (range 30–1725) pg/mL. Numerical symbols 1–7 represent operations done in 1996–2013, respectively. Pharmacological medication of SHPT (phosphate binder, active vitamin D) was used in the course of dialysis treatment.

The difference in this patient appearance was striking from 1996 (Figure 2). Obviously maxillary swelling appeared. Frontal forward malformation of the upper jaws was presented. Teeth were irregularly shaped and located. Skull tomography showed bone density changes. Chest X-ray examination showed osteofibrous dysplasia in lib. She also had mitral and aortic valves calcifications detected by ultrasonic cardiogram. Bone fracture has not yet occurred so far. Osteoporosis of spine and slight kyphosis caused a decrease of height from 168.0 cm to 163.5 cm. Body mass fell from 57.5 kg to 45.5 kg. Characteristic deformities in uglifying fashion resulted in a diagnosis of SS. She began insecurities about her peculiar appearance and was afraid to look in the mirror. She also suffered from clinical problems including headache, fatigue, pruritus, bone pain, and multiple subcutaneous calcified nodules. However, fingertip changes, hearing loss and other neuropsychiatric disorders such as polyneuropathy, cranial neuropathy, depression and hopeless were undetected.

Figure 2. Facial appearance of the patient: (A) before the year of treatment with intermittent hemodialysis; (B, C, D) in the 22th year of treatment with intermittent hemodialysis.

The patient had a warm, loving and supportive family. Her physical status showed no significant difference compared with other HD patients.

Discussion

SS is a unique entity of SHPT in late and severe CKD with skull and facial changes in uglifying fashion. Although some sporadic cases have been reported of facial bone alterations, the collection of this phenomenon was first described in detail by Sagliker et al. in 2004. Late SHPT, inappropriate treatment modalities due to monetary deficiencies, socioeconomic insufficiencies and iatrogenic mistreatments may play the major part in the genesis of SS.6

Previous study suggested that osteoporosis was caused by SS per se. Laboratory text, such as thyroid function, growth hormone levels and sex hormone levels showed no striking differences in SS.4 But SS patients had typical biochemical serum calcium values averaging 6–7 mg/dL, phosphate levels of 7–8 mg/dL, increased levels of alkaline phosphatase (ALP) (120–240 U/L), and at least 3.5 times greater values than normal for intact PTH levels (180–240 pg/mL by immunoradiometric assay) before entry to HD treatments.1 However, ALP in this patient was within the normal range. Study from China–Japan Friendship Hospital showed that craniofacial changes were exclusively at specific sites with the maxillary body enlarged especially in sagittal and vertical directions, the anterior part of mandibula increased in the vertical direction; and gender, age, dialysis age and higher serum ALP level might be the risk factors for SS. The exact mechanism underlying SS is not sure. SS patients might have genetically disordered during their childhood and present with CKD later on. An international study suggested that GNAS1 genes missense mutations rather than chromosomal abnormalities or calcium-sensing receptor gene abnormalities would be considered for the genesis of SS.4 However, no matter what mechanism could be, it is disastrous for appearance and psychological health.

For this patient, HD treatment was sufficient according to result of urea reduction rate (URR) ≥70% and single-pool Kt/V (spKt/V) ≥1.4. Since she had been on HD in the early 1990 s, factors contributing to SS might be insufficient emphasis on dietary concerns (such as dietary phosphate restriction), lack experience in management of mineral metabolism, shortage in agents, patient adherence and acceptance. It is noteworthy that SS developed in this patient after complete loss of RRF. The presence of RRF, even at a low level, contributes to adequacy of dialysis, quality of life and mortality. Previous studies have demonstrated that RRF is associated with significant capacity to excrete phosphate.7 The preservation of urinary phosphorus excretion has the ability to control serum phosphorus levels and total body phosphorus content and lastly on the ability to control PTH levels, which might be a benefit to postpone the development of SS. However, RRF is minimal in many patients treated with HD, which might be the reason that most SS developed in HD patients. Unfortunately, data on PTH level before RRF loss in this patient was lost, and the impact of RRF decline on PTH level needs further investigation.

In the past years, a great advance has been made in the treatment of SHPT. For example, calcimimetic agents were introduced to slow or stop progression of bone changes which may be the hope for making SS a history. Some vigorous treatments, such as renal transplantation, PTX, also seem to be effective for whom pharmacological treatment failed to adequate regulation of parathyroid function. However, the patient in this case lost her renal graft just after the kidney transplantation due to acute rejection. Spending a long time on dialysis before transplantation, health problems caused by dialysis over time might be the reason, and the severity of preexisting SPHT also should be taken into account, which seemed to increase the risk of graft loss among transplanted patients. Related matters about renal transplantation for patients with SS need further discussion. As for PTX, it should not be put off when patients failed to respond to pharmacological therapy. In time PTX may control and partially ameliorate bone changes shown in SS. However, relapses of SHPT caused by residual parathyroid tissue left in the neck, hyperplastic grafted tissue, undetected supernumerary gland during surgery or the multiple ectopic glands are relatively frequent in HD patients. In this case, PTX could effectively treat SS by SHPT, however, in view of the frequent recurrence, tPTX without autotransplantation maybe the better option. Furthermore, localization of the parathyroid tissue prior to operation also is necessary.

Though it is possible that such patients could survive long-term with dialysis, the inability to correct all the changes can be catastrophic for those patients. Treatment must begin early and be the appropriate treatment given in specialized centers with sophisticated skills.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.