Download Primary hyperparathyroidism presenting with acute renal failure in a

Primary hyperparathyroidism presenting with acute renal failure in a patient
with adenocarcinoma of the colon after surgery
Ching-Fang Wu1, MD, Chin-Chi Kuo1, MD, Vin-Cent Wu1, MD, Yung-Ming Chen1, MD,
PhD
1
Division of Nephrology, Department of Internal Medicine, National Taiwan University
Hospital, College of Medicine, National Taiwan University, Taipei, 100, TAIWAN
Correspondence to: Yung-Ming Chen, M.D.,
Department of Internal Medicine, National Taiwan University Hospital,
College of Medicine, National Taiwan University,
#7, Chung-Shan South Road, Taipei 100, Taiwan
Phone:
(886)-2-2312-3456 ext. 5993; Fax:
E-mail:
[email protected]
(886)-2-2322-2955
Running title: hypercalcemia and acute renal failure in a cancer patient
Reprint request address: #17, Lane 66, Yan-Ping North Road, sec 1, Taipei, 103, Taiwan
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Abstract
Not all hypercalcemia occurring in patients with malignancy is mediated by humoral
hypercalcemia of malignancy or osteolytic mechanism. Here we report a case of colon
adenocarcinoma presenting with recurrent hypercalcemia caused primarily by primary
hyperparathyroidism. This 83-year-old woman initially had drowsy consciousness and
vomiting for 2 days. She had just received right hemicolectomy and ileostomy for stage IV
colon adenocarcinoma 3 months before the episode. Laboratory data showed elevated blood
urea nitrogen and serum creatinine, hyperkalemia, metabolic acidosis, and hypercalcemia.
Serum intact parathyroid hormone level was 5-fold above normal.
99m
Tc-sestamibi
scintigraphy combined with single photon emission computed tomography disclosed a hot
spot at left lower thyroid bed. Primary hyperparathyroidism was diagnosed. Her
consciousness and renal function recovered completely after medical treatment. Surgical
removal was not performed given the poor performance status of the patient. However,
recurrent hypercalcemia with acute renal failure complicated with sepsis occurred after the
discharge until she died. This report highlights the diverse etiologies of hypercalcemia in
patients with malignancy, and exemplifies primary hyperparathyroidism as a potential cause
of hypercalcemia in cancer patients.
Key word: hyperparathyroidism, primary; kidney failure, acute; hypercalcemia; colonic
neoplasms
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摘要
癌症病人高血鈣的原因並不光是因為腫瘤細胞分泌副甲狀腺荷爾蒙相關蛋白或有
腫瘤轉移至骨頭形成蝕骨病變，在這邊我們報告一位有反覆發生高血鈣的大腸癌病例其
高血鈣原因是原發性副甲狀腺機能亢進。這位八十三歲女性起初以兩天的嗜睡和嘔吐為
表現，在三個月前才剛因為第四期大腸癌接受右結腸切除和迴腸造口術，實驗室檢查發
現血清尿素氮、肌酸酐和鉀離子過高、代謝性酸中毒和血鈣過高，血清副甲狀腺濃度是
正常上限的五倍。鎝-99m-sestamibi 核醫檢查併單光子放射斷層攝影發現左邊甲狀腺部
位有一亮點。經由以上檢查認定病人有原發性副甲狀腺機能亢進。病人的意識和腎功能
在藥物治療後恢復正常，沒有接受手術治療的原因是因為病人體能無法負荷，然而從這
次出院到她死亡的期間多次發生高血鈣、急性腎衰竭合併敗血症的情況。這個病例提醒
我們癌症病人高血鈣原因的多元性，也告訴我們原發性副甲狀腺機能亢進也是其中一不
能忽視的原因。
關鍵字：原發性副甲狀腺機能亢進、急性腎衰竭、高血鈣、大腸癌
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Introduction
Hypercalcemia is a common complication in patients with malignancy. It had been reported
to occur in 20-30% patients with a malignancy at some time during their disease course(1). A
restrospective study in 1990 found that it signified a very poor prognosis, with approximately
50% of patients dying within 30 days(2). Hypercalcemia associated with malignancy can be
classified into 4 types: 80% is due to humoral hypercalcemia of malignancy (HHM) through
typically parathyroid hormone (PTH)-related peptides, 20% is due to extensive osteolytic
lesions due to tumor invasion, and rarely is due to ectopic iPTH secretion or secretion of
1,25-OH2-vitamin D production(3). However, hypercalcemia occurring in patients with
malignancy cannot be fully accounted for by the above mechanisms. In this report, we
presented a case of colon adenocarcinoma manifesting primary hyperparathyroidism (PHP)
induced recurrent hypercalcemia which exacerbated renal function.
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Case Report
A 83-year-old woman was diagnosed as having diabetes mellitus, hypertensive
cardiovascular disease and dyslipidemia for 10 years. Three months earlier, she underwent
right hemicolectomy and ileostomy for mechanical ileus caused by a transverse colon
adenocarcinoma, T4N2M1, stage IV. Peritoneal seeding was also noted during operation. Her
daily medications were reviewed and the relationship between the drugs and hypercalcemia
could not be established.
She was sent to our emergency department due to progressive drowsy consciousness, poor
appetite, vomiting, and decreased urine output for 2 days. On examination, body temperature
was 35.1℃, blood pressure was 85/50 to 102/38 mmHg, and pulse rate was regular at
40-70/min. Electrocardiogram demonstrated intermittent junctional bradycardia. Glasgow
coma scale was E4M6V4. Other physical and neurological examinations were unremarkable
except dry skin turgor and mucosa. Lab data were as follows: albumin (Alb) 48.4 g/L (4.84
g/dL), blood urea nitrogen (BUN) 74.1 mmol/L (207.7 mg/dL), creatinine (Cre) 778 μmol/L
(8.8 mg/dL), potassium (K) 7.4 mmol/L, calcium (Ca) 3.65 mmol/L, magnesium (Mg) 1.34
mmol/L, and arterial pH/ PaCO2/ PaO2/ HCO3/ BE 7.14/ 19.2/ 201.1/ 6.2/ -21.9. Renal
ultrasound revealed normal kidney size without hydronephrosis or urolithiasis. Acute renal
failure (ARF) induced by hypercalcemia and superimposed dehydration was considered. Due
to unstable hemodynamics, the patient received continuous venovenous hemofiltration for 1
5
day. Hydration with 0.9% saline (>2,500ml/day) and intravenous infusion of 4mg Zolendronic
acid were also administered. Her consciousness immediately recovered, and urine output also
increased along with normalization of renal function and serum calcium level. Initial workups
for hypercalcemia revealed a serum phosphorus (P) level of 2.29 mmol/L (7.1 mg/dL) and
intact
parathyroid
hormone
(iPTH)
hyperparathyroidism was impressed.
level
of
159
ng/L (159
pg/mL).
Primary
99m
Tc-sestamibi (MIBI) scintigraphy and parathyroid
single photon emission computed tomography (SPECT) on the 10th day showed a focal hot
area at left lower thyroid bed. Parathyroid adenoma was suspected. (Figure 1) Two weeks
later, the patient’s renal function and serum Ca level maintained normal though P level
remained low (0.77 mmol/L or 2.4 mg/dL) and iPTH level remained elevated (337 ng/L or
337 pg/mL). Because of poor performance status, she refused to undergo surgical removal of
the suspected adenoma and was discharged on the 22nd hospital day with decreased activities
of daily living.
However, similar episodes recurred in the following 10 weeks. During the second
admission, the acute kidney injury responded well to adequate hydration (Cre 866μmol/L or
9.8 mg/dl to 80μmol/L or 0.9 mg/dl). In contrast, hypercalcemia and hyperparathyroidism
persisted accompanied by low serum P level (0.77 mmol/L or 2.4 mg/dL). The patient finally
did not survive the third admission complicated with uncontrolled sepsis. The total clinical
course is summarized in Figure 2.
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Discussion
As exemplified in our case, PHP had been identified in patients with various
malignancies(3), and up to 10% of patients with PHP may harbor a concomitant
malignancy(4). Farr reported that the frequencies of breast, gastric and colon cancer
associated with PHP were 16%, 10% and 6% respectively(5). These associations were
significantly higher than those in the general population. In a hospital-based survey, 4% of
cancer patients with hypercalcemia were found to have coexistent PHP, whereas the
prevalence of hyperparathyroidism was about 0.1% in the general population(6). Despite of
some conflicting results of the association from several retrospective record-linkage
studies(7-11), PHP has been mostly linked with breast, kidney, colon and squamous skin
cancer even after correction for parathyroidectomy(7-10). It has been suggested that the same
genetic mechanism or environmental influence is responsible for the association between PHP
and malignancy(10). On the other hand, humoral hypercalcemia is rarely associated with
colon adenocarcinoma(12). It leads to the conclusion that PHP should always be considered as
the most likely cause of hypercalcemia in patients with colon adenocarcinoma.
Recently the presentations of PHP have changed. In the United States and many other
developed countries, three-fourths of patients had no symptoms or signs(13-15). However,
still a few patients with PHP, however, develop parathyroid crisis, which is characterized by
severe hypercalcemia (greater than 3.5 mmol/L or 14 mg/dL), and marked symptoms of
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hypercalcemia, especially that of central nervous system dysfunction. This peculiar subset of
patients tends to be younger than 40 years of age(16) and have 20 times higher than normal
PTH level(17). For the present patient, she had severe hypercalcemia but did not completely
fulfill the criteria of parathyroid crisis. The age was older and exhibited a relatively lower
iPTH level as compared to previous observations. Because there was no evidence supporting
the presence of HHM, we surmise that factors such as dehydration and immobilization might
have contributed to her severe hypercalcemia.
Actually this patient was indicated to receive parathyroidectomy due to severe
hypercalcemia and recurrent ARF. But how do we care these symptomatic patients without
surgical intervention? In addition to keeping adequate hydration and avoidance of nephrotoxic
drugs, local ethanol injection of suspected parathyroid adenoma or calcimimetic such as
cinacalcet, which is not available here, should be considered.
In conclusion, we have reported a patient with colon cancer experiencing PHP-induced
hypercalcemia and the resultant ARF. The complete recovery of renal function in this case
underscores the importance of identifying hypercalcemia secondary to benign diseases such
as PHP, as a cause of acute renal failure in patients with malignancy especially colon
adenocarcinoma.
Acknowledgement and Declaration:
For all authors, there was no conflict of interest to declare.
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Funding
This work was supported by grants from the Ta-Tung Kidney Foundation and the Mrs.
Hsiu-Chin Lee Kidney Research Fund, Taipei, Taiwan.
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Figure 1.
99m
Tc-sestamibi (MIBI) scintigraphy combined with single photon emission
computed tomography shows a focal hot area of accumulated 99mTc-MIBI at left lower thyroid
bed, which is compatible with left lower parathyroid adenoma
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Figure 2. This figure reveals the change of renal function, serum calcium level and intact
parathyroid hormone level in the patient. Day 1 refers to the first admission day of the first
admission. (iPTH 100 pg/mLl = 100 ng/L; Cre 1mg/dL = 88 μmol/L)
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