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Year : 2015  |  Volume : 58  |  Issue : 4  |  Page : 487-490
Functional parathyroid cystic adenoma: A rare cause of hypercalcemic crisis with primary hyperparathyroidism


1 Department of Pathology, Vydehi Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India
2 Department of Endocrine surgery, Vydehi Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India
3 Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India
4 Department of General Medicine, Vydehi Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India

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Date of Web Publication4-Nov-2015
 

   Abstract 

We discuss a case of primary hyperparathyroidism caused by a giant cystic parathyroid adenoma presenting with neck swelling and hypercalcemic crisis. Fine-needle aspiration cytology of presumed thyroid swelling from one of the two sites aspirated yielded clear fluid but was not attributed to parathyroid pathology. Elevated serum calcium and intact parathormone (iPTH) levels suggested preoperative parathyroid pathology. Ultrasound neck and sestamibi scan for parathyroid localization were not conclusive. Due to resistant hypercalcemia, the patient underwent emergency bilateral neck exploration and excision of the identified left superior parathyroid cyst along with total thyroidectomy. Monitoring of intra-operative iPTH helped complete removal of hyperfunctioning parathyroid tissue. Histopathological examination confirmed the parathyroid cyst. Cystic parathyroid adenoma should be considered in the differential diagnosis of cystic neck lesions.

Keywords: Hypercalcemic crisis, parathyroid adenoma, parathyroid cyst, primary hyperparathyroidism

How to cite this article:
Sumana B S, Sabaretnam M, Sarathi V, Savith A. Functional parathyroid cystic adenoma: A rare cause of hypercalcemic crisis with primary hyperparathyroidism. Indian J Pathol Microbiol 2015;58:487-90

How to cite this URL:
Sumana B S, Sabaretnam M, Sarathi V, Savith A. Functional parathyroid cystic adenoma: A rare cause of hypercalcemic crisis with primary hyperparathyroidism. Indian J Pathol Microbiol [serial online] 2015 [cited 2019 Dec 6];58:487-90. Available from: http://www.ijpmonline.org/text.asp?2015/58/4/487/168847



   Introduction Top


Functional parathyroid cysts (FPC) are rare lesions usually located in the neck and are frequently omitted in differential diagnosis of cystic cervical masses.[1],[2] FPC can present with signs and symptoms of primary hyperparathyroidism (PHPT) and/or compressive symptoms.[1],[3] Hypercalcemic crisis is a very rare and potentially life-threatening presentation of a FPC. Early diagnosis and aggressive treatment, including expeditious parathyroidectomy is required to avoid a lethal course.[4],[5]


   Case Report Top


A 46-year-old female presented to the emergency room in September 2013 with generalized weakness and anorexia since 1-month, fever associated with chills, burning, and increased frequency of micturition since 15 days, vomiting since 10 days and puffiness of face and swelling of the lower limbs since 7 days. Patient was a diagnosed case of type 2 diabetes mellitus and systemic hypertension for last 10 years, well-controlled by drugs. In 2012, the patient was diagnosed with right nephrolithiasis and managed conservatively. History of hoarseness of voice was noted since 1-month. No significant family history. No history of radiation exposure.

On physical examination, she was febrile and blood pressure was 160/80 mmHg. Neck revealed a 6 cm × 4 cm sized nodular swelling in the anterior part with left side palpable more than right, firm-hard in consistency, moving with deglutition.

Fine-needle aspiration cytology (FNAC) sample of the presumed thyroid mass was procured from two different sites. One site yielded about 5 ml clear liquid aspirate, the cytospin smears of which were acellular on microscopy, whereas the hemorrhagic aspirate from the other site suggested nodular goiter on microscopy.

Hemogram revealed neutrophilic leukocytosis. Urine examination revealed plenty of pus cells per high power field. There was no evidence of nephrolithiasis or pyelonephritis. The urinary tract infection was treated with intravenous antibiotics. She had normal urine output but serum creatinine was elevated 3.8 mg/dl (normal range 0.4–1.0 mg/dl).

Further evaluation revealed hypercalcemia (serum calcium of 16.9 mg/dl) (normal range: 8.5–10.2 mg/dl), hypoalbuminemia (serum albumin: 3.1 g/dl) and slightly elevated serum phosphorus of 4.8 mg/dl. Pancreatic enzymes and thyroid function tests were normal. X-rays of skull and hands showed osteolytic lesions.

Subsequent work up of the patient revealed plasma level of intact parathormone (iPTH) to be 880.1 pg/ml (normal range: 12–88 pg/ml). Ultrasound neck revealed a multinodular goiter with suspicion of thyroid cyst/parathyroid cyst. She underwent a 99mTc-sestamibi parathyroid scan, which showed delayed washout from the multinodular goiter without clear cut localization of the parathyroid adenoma [Figure 1]a and b.
Figure 1: (a and b) 99mTc sestamibi parathyroid scan demonstrating delayed washout from the multinodular goiter

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She was started on aggressive intravenous hydration and subcutaneous calcitonin 100 IU thrice a day. Corrected serum calcium transiently decreased to 14.2 mg/dl after 48 h (hospitalization day 4) with a concomitant decrease in serum creatinine to 1.71 mg/dl. However, on day 5, corrected serum calcium started rising again and on day 6, it was 17.2 mg/dl; 60 mg intravenous pamidronate was administered. On day 7 (12 h from pamidronate administration) patient's sensorium was altered with a corrected serum calcium of 18.59 mg/dl.

She was taken for emergency bilateral (since the imaging was discordant) neck exploration. Intra-operatively, she was found to have a left superior parathyroid cyst which was excised [Figure 2] and also total thyroidectomy was done, since the thyroid had multiple nodules in both lobes. The surgical cure was confirmed by intra-operative parathormone (IOPTH) measurement, which had curative fall according to Miami criterion and also symptomatic hypocalcemia. The iPTH levels were measured by a paramagnetic particle chemiluminiscent immunoassay using the Access Immunoassay Systems having both routine and intra-operative modes.
Figure 2: Intra-operative finding showing the parathyroid cyst in the left superior parathyroid region

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The specimen of the cystic lesion measuring 6 cm × 4 cm × 3 cm and weighing 21 g showed a smooth exterior surface with minimal hemorrhage and no significant adhesions. On sectioning the lesion was cystic, exuded clear fluid. Cyst wall surface on the inside was irregular, soft and reddish brown in color [Figure 3]. Microscopically, substantial rim of viable parathyroid tumor tissue surrounded by a thin fibrous capsule and a central cystic lumen was noted. Adipose tissue was seen outer to the fibrous capsule [Figure 4]. The tumor tissue was mainly composed of chief cells in micro-cystic and micro-glandular patterns [Figure 5]. A delicate vascular network traversing the tumor was present. The tumor cells displayed round to oval nuclei, heavy nuclear chromatin and abundant clear to slightly eosinophilic cytoplasm. No histologic criteria of malignancy were seen. The histopathologic analysis in correlation with the clinical and intra-operative findings was compatible with a cystic parathyroid adenoma. Histopathology of thyroid specimen revealed features of nodular hyperplasia.
Figure 3: Cut surface of the encapsulated tumor showing cystic change

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Figure 4: Photomicrograph showing solid and cystic area (H and E, ×40)

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Figure 5: Photomicrograph showing solid area with chief cells in micro-cystic and micro-glandular pattern (H and E, ×100)

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Postoperatively, the patient had transient hypoparathyroidism for 6 weeks which was treated with calcium and 1,25-(OH)2 Vitamin D supplementation. Follow-up biochemical analyses of total serum calcium and iPTH levels, performed 3 months, 6 months and 1-year later were normal.


   Discussion Top


This case highlights the rare presentation of cystic parathyroid adenoma with hypercalcemic crisis. It also exemplifies the difficulties in the preoperative diagnosis of a parathyroid cyst and the importance of FNAC and IOPTH monitoring for a successful management of the patient.

PHPT is an uncommon disease which is caused by different pathologic lesions of the parathyroid glands. The most common causes of PHPT are solitary parathyroid adenoma (approximately 85%), multiple adenomas or primary parathyroid hyperplasia (approximately 14%), and parathyroid carcinoma (approximately 1%).[6],[7] Cystic parathyroid adenoma is not a distinct histopathologic diagnosis but is an uncommon feature of parathyroid adenoma. Most of the parathyroid adenomas are functional, but are very rarely cystic. They account for about 1–4% of all parathyroid adenomas and 1–2% of patients with PHPT.[8]

Parathyroid cysts are traditionally categorized into functional and nonfunctional (true) parathyroid cyst. Only about 300–350 cases of parathyroid cysts have been reported in the world literature.[1],[9],[10],[11] Some authors report that FPCs are more common than the non-FPC [7],[9] which differs from most other studies in the literature.[1],[2],[3],[10] The four criteria defining a FPC are: (1) Preoperative clinical and biochemical evidence of hyperparathyroidism, (2) intra-operative evidence of normal remaining parathyroid glands, (3) histologic identification of parathyroid tissue within the cyst wall, and (4) postoperative correction of hypercalcemia.[1] Our case satisfied all these criteria.

FPC may arise as the histologic degeneration of an adenoma or a hyperplastic gland.[9],[10] It is opined that all FPCs are actually parathyroid adenomas with cystic degeneration.[9] Parathyroid cyst is often confused with thyroid cysts clinically and radiologically.[2],[12] It is important to remember parathyroid cyst (functional/nonfunctional) in the differential diagnosis of neck mass.

FNAC is an established test as afirst line investigation in the evaluation of neck masses. Our patient having both thyroid and parathyroid lesions presented as neck swelling, which on examination was perceived to be nodular enlarged thyroid; the FNAC performed on both sides were considered to be from thyroid, even though actually from the left side we had aspirated the parathyroid cyst and obtained clear fluid. A similar case has been reported, wherein the preoperative FNAC analysis of clear fluid filled cystic nodular lesion on right lobe of thyroid could not define the origin of the lesion.[2] Few other studies have also mistaken parathyroid cyst for a thyroid cyst because of a turbid or colored fluid aspirate,[9] but unlike in our case there was no concomitant thyroid pathology. Aspiration of clear colorless fluid from a neck lesion should suggest the possibility of a parathyroid cyst.[2],[10],[13] Other studies observe that turbid or colored fluid in an aspirate does not exclude the diagnosis of parathyroid cyst, further recommending iPTH analysis in all cystic neck masses regardless of fluid character.[9] Assay of iPTH levels in cyst fluid helps to differentiate parathyroid cyst from other cystic neck lesions and in case of elevated iPTH levels, further investigation of the patient for PHPT will be able to characterize the cyst as FPC or non-FPC.

Cervical ultrasound examination and sestamibi scan performed for preoperative localization of parathyroid are indicative, but not always conclusive in cystic neck lesions.[2],[8],[12] The advent of rapid IOPTH assay has decreased the need of intra-operative frozen section diagnosis which has inherent limitations except in recognizing parathyroid carcinoma to permit radical excision. If the decline in the plasma levels of PTH after excision of the enlarged parathyroid gland is ≥50% compared to the highest baseline hormone level (preincision or preexcision), it can be assumed that all hyperfunctioning parathyroid tissue has been successfully removed (Miami criterion).[14]

Rarely, FPC manifests with hyperparathyroidism induced hypercalcemic crisis (HIHC)[3] as in our case. HIHC is characterized by profound hypercalcemia (serum calcium ≥14 mg/dl) along with deterioration of central nervous system, cardiac, gastrointestinal, and renal functions.[4] A systematic review of publications from 1958 to 2011 has found a total of 499 reported cases of HIHC.[5] A single parathyroid adenoma [4] often associated with a micro-cystic histopathological pattern was noted as the most common cause of HIHC.[15] In our case a prominent micro-cystic pattern along with micro-glandular pattern was noted.

In patients with very high serum calcium and PTH levels, huge size of cystic adenoma and palpable neck mass (as in our patient) a parathyroid carcinoma has to be borne in mind and ruled out on histopathology.[7]


   Conclusion Top


FPCs may present as hypercalcemic crisis. Parathyroid cyst although a less common cause of cervical masses, should be considered in the differential diagnosis. FNAC is an important diagnostic tool and assay of iPTH levels in aspirate fluid will differentiate a parathyroid cyst from thyroid cyst. Parathyroid cysts most often present with negative sestamibi scan. IOPTH monitoring helps in surgical cure.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
   References Top

1.
Khan A, Khan Y, Raza S, Akbar G, Khan M, Diwan N, et al. Functional parathyroid cyst: a rare cause of malignant hypercalcemia with primary hyperparathyroidism – A case report and review of the literature. Case Rep Med 2012;2012:851941.  Back to cited text no. 1
    
2.
da Silva DA, Márcia CM, Lúpercio LB, Renato AG, Antônio SF, Conceição AC. Parathyroid cysts: diagnosis and treatment. Rev Bras Otorrinolaringol 2004;790:840-4. Available from: http://www.scielo.br/scielo.php?script=sci_arttext and pid=S0034-72992004000600024 and lng=en. [Last cited on 2014 Dec 09].  Back to cited text no. 2
    
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Spyridon K, Ioannis K, Panagiotis A, Vasilios P, Th K, Nikolaos P, et al. Functional parathyroid cyst as a rare cause of primary hyperparathyroidism: A case report. J Arthritis 2013;2:2. Available from: http://www.omicsgroup.com/jarthritis/journal/2167-7921.1000107. [Last cited on 2014 Dec 14].  Back to cited text no. 3
    
4.
Singh DN, Gupta SK, Kumari N, Krishnani N, Chand G, Mishra A, et al. Primary hyperparathyroidism presenting as hypercalcemic crisis: Twenty-year experience. Indian J Endocrinol Metab 2015;19:100-5.  Back to cited text no. 4
    
5.
Gurrado A, Piccinni G, Lissidini G, Di Fronzo P, Vittore F, Testini M. Hypercalcaemic crisis due to primary hyperparathyroidism – A systematic literature review and case report. Endokrynol Pol 2012;63:494-502.  Back to cited text no. 5
    
6.
Chan JK. Tumors of the thyroid and parathyroid glands. Part B. The parathyroid gland. In: Fletcher CD, editor. Diagnostic Histopathology of Tumors. 4th ed. Philadelphia: Saunders Elsevier; c2013. p. 1273-93.  Back to cited text no. 6
    
7.
Asghar A, Ikram M, Islam N. A case report: Giant cystic parathyroid adenoma presenting with parathyroid crisis after Vitamin D replacement. BMC Endocr Disord 2012;12:14.  Back to cited text no. 7
    
8.
Johnson NA, Yip L, Tublin ME. Cystic parathyroid adenoma: sonographic features and correlation with 99mTc-sestamibi SPECT findings. AJR Am J Roentgenol 2010;195:1385-90.  Back to cited text no. 8
    
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McCoy KL, Yim JH, Zuckerbraun BS, Ogilvie JB, Peel RL, Carty SE. Cystic parathyroid lesions: functional and nonfunctional parathyroid cysts. Arch Surg 2009;144:52-6.  Back to cited text no. 9
    
10.
Guner A, Karyagar S, Ozkan O, Kece C, Reis E. Parathyroid cyst: the forgotten diagnosis of a neck mass. J Surg Case Rep 2011;2011:4.  Back to cited text no. 10
    
11.
Khang AR, Kim EK, Nam EY, Byeon SJ, Kim JH, Ohn JH, et al. Primary hyperaparathyroidism due to cystic parathyroid adenoma not detected on 99mTc-Sestamibi Scan. Endocrinol Metab 2012;27:83-8. Available from: http://www.enm-kes.org. [Last cited on 2014 Nov 09].  Back to cited text no. 11
    
12.
Davies M, Middleton S, Mellor S. Mistaken identity: Cystic parathyroid adenoma masquerading as a Goitre. Internet J Surg 2001;3:3. Available from: http://www.ispub.com/IJS/3/2/11415. [Last cited on 2014 Dec 09].  Back to cited text no. 12
    
13.
Jayaram G, Orell SR. Thyroid. In: Orell SR, Sterrett GF, editors. Orell and Sterretts's Fine Needle Aspiration Cytology. 5th ed. Gurgaon: Elsevier Limited; 2012. p. 118-55.  Back to cited text no. 13
    
14.
Guerrero MA, Clark OH. A Comprehensive review of intraoperative parathyroid hormone monitoring. World J Endocr Surg 2010;2:21-7.  Back to cited text no. 14
    
15.
Starker LF, Björklund P, Theoharis C, Long WD 3rd, Carling T, Udelsman R. Clinical and histopathological characteristics of hyperparathyroidism-induced hypercalcemic crisis. World J Surg 2011;35:331-5.  Back to cited text no. 15
    

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Correspondence Address:
B S Sumana
No 15, Renuka, Ninth Main, Eleventh Cross, BDA Layout, HAL Third Stage, Jeevanbhima Nagar, Bengaluru - 560 075, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.168847

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    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

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