80 year old female with parathyroid mass and refractory hypercalcemia. Endorama September 24 th, 2015 Rajesh Jain

Size: px

Start display at page:

Download "80 year old female with parathyroid mass and refractory hypercalcemia. Endorama September 24 th, 2015 Rajesh Jain"

Stewart Pope
5 years ago
Views:

$80 year old female with parathyroid mass and refractory$

1 80 year old female with parathyroid mass and refractory hypercalcemia Endorama September 24 th, 2015 Rajesh Jain

2 HPI 80 F with pulmonary hypertension, rheumatic mitral stenosis, atrial fibrillation on coumadin, presented to OSH. 07/19 fall while going downstairs, hit her head 07/20 husband notes she was slow to respond, eventually minimally responsive, unable to get out of car. 911 called, patient vomited en route to hospital, complaining of HA. Bradycardic at presentation to OSH. CT head showed large subdural hematoma. 07/21 Craniotomy and evacuation. Initial labs show elevated calcium to 11.7

3 Extended History PMH: Atrial fibrillation, severe rheumatic mitral stenosis, pulmonary hypertension PSH: Cholecystectomy Meds: Digoxin mg qday, warfarin 5 mg qday Allergies: Ciprofloxacin Social Hx: Lives with husband. Never smoker, no alcohol use. Previously had refused mitral stenosis repair Family History: Sister with breast cancer. Otherwise, noncontributory

4 Physical Exam per OSH on Day 5 T 36.2, P 93, BP 146/79, R 21, SpO2 100% R 20 Wt 62 kg, BMI 23.6 Gen: No acute distress HEENT: EOMI, oropharynx clear Neck: supple, +neck mass Lung: Normal respiratory effort, course breath sounds Chest wall: no tenderness or deformity CV: Irregularly irregular Abdomen: Soft, non-tender, BS active Extremities: Normal, atraumatic, no cyanosis Neuro: Lethargic

5 Labs at OSH on Day

6 Differential Diagnosis? Parathyroid adenoma or hyperplasia Parathyroid carcinoma Hypercalcemia of malignancy Medication effects (e.g. thiazides, lithium) Familial hypocalciuric hypercalcemia Rare: thyrotoxicosis

7 Labs at OSH on Day PTH Vit D 19

8 OSH Management Corrected Calcium HD x 1, Sensipar 60 Mg BID, Calcitonin 200 Units BID 13 Corrected Calcium IVF 150 cc/hr, lasix 20 mg IV q12h, Sensipar 30 mg BID, Zoledronic Acid 4 mg IV Hospital Day

9 Transfer to UCMC Corrected Calcium at arrival was 12.0 but quickly went down to 11.1 with IV fluids started by the primary team Initial Endocrine Recommendations Sensipar 60 mg BID Lasix 20 mg IV q12h with IVF Check TFTs (later came back WNL) Obtain imaging, concern for parathyroid carcinoma

10 Neck CT

It likely represents a parathyroid adenocarcinoma with apparent invasion of the adjacent trachea and esophagus as

11 Neck CT An infiltrative mass in the right tracheoesophageal groove measures up to 4 cm and appears to invade the adjacent right lobe of the thyroid, tracheal wall, and esophagus. It likely represents a parathyroid adenocarcinoma with apparent invasion of the adjacent trachea and esophagus as well as what may represent bland or tumor thrombus in the right internal jugular vein Prominent right level 6 and upper mediastinal lymph nodes may represent metastatic disease

12 Parathyroid carcinoma Very rare! 5.73 per 10,000,000 Typically present age and occurs equally in men and women May occur sporadically or as part of a genetic syndrome Lee et al. Trends in the incidence and treatment of parathyroid cancer in the United States. Cancer 2007;109.9: Wei and Harari. Parathyroid carcinoma: update and guidelines for management. Curt Treat Options Oncol 2012;13:11-23.

Diagnosis Shares similar clinical features of benign disease Higher PTH levels and palpable neck mass should raise suspicion 3 rd versus 2 nd

13 Diagnosis Shares similar clinical features of benign disease Higher PTH levels and palpable neck mass should raise suspicion 3 rd versus 2 nd generation PTH assays FNA not recommended Wei and Harari. Parathyroid carcinoma: update and guidelines for management. Curt Treat Options Oncol

14 Cavalier, et al. JCEM 2010;95.8: Parathyroid carcinomas oversecrete amino- PTH, which is not detected on 2 nd generation PTH assays, but cross reacts with newer 3 rd generation PTH assays In 24 parathyroid carcinoma patients & 245 controls, ratio > 1 had 83% sensitivity and 100% specificity

15 PTH assay at UCMC PTH assay at UCMC is a second generation assay Unfortunately, 3 rd generation is not widely available However, different second generation kits have different avidity to amino-pth and a ratio of these PTH methods may, in theory, provide similar information

16 Treatment & Prognosis Primarily surgical, with removal of any additional tissues involved, such as ipsilateral thyroid lobe, trachea, or esophageal wall Chemotherapy and radiation generally ineffective No standard chemo regimen exists, only case reports Palliative therapies: Alcohol ablation Prognosis: persistent or recurrent disease in more than 50%, mean time of recurrence years, neither tumor size nor lymph node status are significant prognostic factors Mortality often due to complications and end-organ damage from intractable hypercalcemia (e.g. renal failure)

17 Hundahl et al. Two hundred eighty six case of parathyroid carcinoma treated in the U.S. between : a national cancer data base report. Cancer 1999;86: Survival Percent survival Years from dx

18 Case continued Neurosurgery recommends ideally 4 weeks prior to other surgeries to allow for residual brain edema to subside

19 Calcium trend Corrected calcium over time What now? Pamidronate 60 mg IV Sensipar 60->90 mg BID Corrected calcium Slowly improving MS More confused & lethargic Hospital Day

20 Calcium trend Pamidronate 60 mg IV Corrected calcium over time Sensipar 90 mg BID Pamidronate 90 mg Sensipar 90 mg TID Calcitonin 250 units bid Sensipar 90 mg TID Calcitonin 250 units BID NS + Lasix 40 mg po q12h S/p 3 doses BSP Corrected calcium Mental status Hospital Day

21 Refractory Hypercalcemia Options? Zoledronic Acid Denosumab Dialysis???

22 Dialysis? Effective but transient Camus et al. Calcium free hemodialysis: experience in the treatment of 33 patients with severe hypercalcemia. Intens Care Med 1996;22:

23 Dialysis? And potential for complications

24 Renal consultation Renal was consulted and did not feel there was a need for dialysis. No role for HD: most stores of calcium are in bone, only 1% is in the extracellular compartment and so post-dialysis for a few hours, numbers will look better, but later will again have high levels.

25 Pamidronate vs. Zoledronic Acid 275 patients with cancer and CSC > 12.0 randomized to pamidronate 90 mg, zoledronic acid 4 mg, or zoledronic acid 8 mg Major et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001;19:

26 Denosumab Vellanki et al. Denosumab for management of parathyroid carcinoma-mediated hypercalcemia. JCEM 2013; 99:

27 Refractory hypercalcemia defined as corrected serum calcium > days after treatment with an IV bisphosphonate (pamidronate OR zoledronic acid) Denosumab given on days 1, 8, 15, and 29 and every 4 weeks thereafter By day 10, 21 of 33 patients (64%) achieved corrected calcium of 11.5 or less. Median duration of response was 104 days 10 patients who initially responded relapsed Hu, et al. JCEM 2014;99.9:

29 Calcium after Zoledronic Acid Zoledronic acid 4 mg Corrected calcium over time Corrected calcium Hospital Day

30 Patient finally goes to surgery

31 Patient finally goes to surgery

32 Pathology FINAL PATHOLOGIC DIAGNOSIS A.Right paratracheal mass, biopsy - Hypercellular parathyroid tissue B. Right paratracheal mass, excision - Enlarged hypercellular parathyroid gland (4 cm)

33 PTH No intra-operative PTH done but postoperatively, PTH drops to 37. Due to concern for hungry bone syndrome, patient transferred to the ICU.

34 Hungry Bone Syndrome No standard definitions but refers to profound and prolonged (longer than 4 th post-op day) hypocalcemia following parathyroidectomy Incidence of 13% in one series of primary hyperparathyroidism (n=198) Fall in serum calcium due to functional or relative hypoparathyroidism, leading to bone formation and influx of calcium into bone, as well as less PTH-mediated 1,25-OH vitamin D formation & decreased Ca absorption/increased excretion

35 Predictors of Hungry Bone Syndrome Brasier and Nussbaum. Hungry Bone Syndrome: Clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med 1988; 84:

36 Predictors of Hungry Bone Syndrome Brasier and Nussbaum. Hungry Bone Syndrome: Clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med 1988; 84:

37 Post-operatively Zoledronic acid 4 mg Corrected serum calcium over time Surgery Corrected serum calcium Hospital Day

38 One retrospective study of 23 patients with primary hyperparathyroidism with similar pre-operative calcium levels, 0 of 6 treated with bisphosphonate developed hungry bone syndrome, while 9 of 17 not treated did Another retrospective case series of 46 patients who received zoledronic acid had only 4% rate of hungry bone syndrome Lee et al. J Bone Miner Metab 2006;24: Witteveen et al. Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endo 2013: 168: R45-53.

39 Case conclusion Patient started on calcium carbonate supplementation 1250 mg BID when her corrected calcium fell below the normal range but never fell <8.0 mg/dl Admission complicated by persistent altered mental status, atrial fibrillation with RVR, requirement for G-tube, and hyperglycemia with tube feeds Discharged to subacute rehab last week

40 References Wei and Harari. Parathyroid carcinoma: update and guidelines for management. Curt Treat Options Oncol 2012;13: Cavalier, et al. Ratio of parathyroid hormone as measured by 3 rd generation and 2 nd generation assays as a marker for parathyroid carcinoma. JCEM 2010;95.8: Hundahl et al. Two hundred eighty six case of parathyroid carcinoma treated in the U.S. between : a national cancer data base report. Cancer 1999;86: Camus et al. Calcium free hemodialysis: experience in the treatment of 33 patients with severe hypercalcemia. Intens Care Med 1996;22: Major et al. Zoledronic acid is superior to pamidronate in the treatment of hypercalcemia of malignancy: a pooled analysis of two randomized, controlled clinical trials. J Clin Oncol 2001;19: Vellanki et al. Denosumab for management of parathyroid carcinoma-mediated hypercalcemia. JCEM 2013; 99: Hu, et al. Denosumab for treatment of hypercalcemia of malignancy. JCEM 2014;99.9: Brasier and Nussbaum. Hungry Bone Syndrome: Clinical and biochemical predictors of its occurrence after parathyroid surgery. Am J Med 1988; 84: Lee et al. Bisphosphonate pretreatment attenuates hungry bone syndrome postoperatively in subjects with primary hyperparathyroidism. J Bone Miner Metab 2006;24: Witteveen et al. Hungry bone syndrome: still a challenge in the post-operative management of primary hyperparathyroidism: a systematic review of the literature. Eur J Endo 2013: 168: R45-53.

76 year-old female presents with muscle cramps. Jess Hwang 12/6/12

76 year-old female presents with muscle cramps Jess Hwang 12/6/12 HPI Worked up for outpatient hypercalcemia Calcium had been 10.3-11.1, PTH ~120 No h/o osteoporosis, CKD, kidney stones Not taking calcium