Synchronous papillary thyroid carcinoma and secondary hyperparathyroidism: Report of cases and review of the literature

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CASE REPORT

Synchronous papillary thyroid carcinoma and secondary hyperparathyroidism: Report of cases and review of the literature

Faissal Tarrass â,^*, Samira Daki â, Meryem Benjelloun â, Benyounes Ramdani â, Mohamed Garbi Benghanem â, Driss Zaid â, Saida Sqalli ^b

aDepartement Nephrology, Ibn Rochd Hospital, 20450 Casablanca, Morocco

b Histo-Pathology laboratory, Ibn Rochd Hospital, 20450 Casablanca, Morocco

Received 2 January 2005; accepted 22 January 2005

Summary Papillary thyroid carcinoma (PTC) is known to occur in association with primary hyperparathyroidism (HPT). A combination of secondary HPT and PTC is a rare event, and of pathogenetic interest. We report two long-term hemodialysis patients in whom invasive PTC was diagnosed at the time of parathyroidectomy for a medically uncontrolled HPT. We suggest that the association of simultaneous pathology of the thyroid and parathyroid glands should be always considered in uremic patients with secondary HPT. A common oncogenic stimulus may have been involved.

KEYWORDS

End-stage renal disease;

Hemodialysis;

Papillary carcinoma;

Parathyroid hormone;

Parathyroidectomy;

Secondary

hyperparathyroidism;

Thyroid cancer

Introduction

Papillary thyroid carcinoma (PTC) is the most common form of thyroid cancer, which usually remains clinically silent until its incidental histologic diag- nosis in autopsy or surgical material.¹ In primary hyperparathyroidism, PTC have been well de- scribed. ² Although, in secondary hyperparathyroidism (HPT), isolated cases have been reported

and are often detected by surgery.^3–6 We report here two cases of thyroid cancer diagnosed at the time of parathyroidectomy for secondary HPT in patients with end-stage renal disease (ESRD).

Case reports Patient I

A 53 years old male, with no personal or family history of neck irradiation, thyroid cancer, or multiple

doi:10.1016/j.ooe.2005.01.001

* Corresponding author. Tel.: +212 66 14 94 94.

E-mail address:faissal76@hotmail.com(F. Tarrass).

Oral Oncology EXTRA (2005)41,74–76

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endocrine neoplasia, was admitted for a surgical parathroidectomy because of medically uncontrolled HPT. The patient had developed ESRD secondary to chronic glomerulonephritis, and had been established on hemodialysis for 119 months at the time of admission. A skeletal survey per- formed two months previously had shown calcifica- tion of the medical sclerosis type affecting arteries of the feet, hands, forearms and pelvis. Investiga- tion showed elevated alkaline phosphatase 1872 iu/l (70–300), grossly elevated PTH 1759 pg/ml (10–75), serum calcium 78 mg/l (85–104), and phosphorus 55 mg/l (25–48). The findings of chest radiography and neck ultrasonography were normal. During the surgical exploration of the neck, two parathyroid glands on the right were in- spected, and the biopsy findings appeared normal.

The upper left parathyroid gland was resected after intraoperative biopsy suggested hyperplasia.

The fourth gland could not be prepared. The final histologic analysis of the resected parathyroid gland confirmed hyperplasia. The thyroid gland had a focus of follicular variant of PTC with a max- imum diameter of 0.7 cm (Fig. 1). No palpable cer- vical lymph nodes were discovered at meticulous intraoperative exploration of the region. Postoper- ative PTH level was 10 pg/ml. Checkups for possi- ble tumor propagation including chest X ray, bone scintigraphy, neck ultrasonography, and scintigra-

phy, have been found to be negative. The patient was given oral thyroid hormone replacement therapy (thyroxine, T4; 100 mg/day). During the sixth and 12th postoperative months a total body scan demonstrated no evidence of any metastatic focus.

Chest radiographs and serum calcium and phosphorus levels remained within normal ranges at regular follow-up visits at 6, 12, 18, and 24 months postoperatively.

Patient II

A 25 years old female with a history of ESRD secondary to chronic pyelonephritis and congenital urogenital malformations, on long-term hemodialysis for 90 months. Nine months prior to her admission, she had biochemical evidence of HPT.

Laboratory investigation demonstrated hypocalce- mia (82 mg/l), hyperphosphatemia (52 mg/l), with a peak PTH level of 1716 pg/ml. Neck ultrasonography was normal. Surgical parathyroidectomy was indicated, because HPT failed to respond to medical therapy comprising alfacalcidol and calcium carbonate. The histological report diagnosed hyperplasia of the parathyroid glands, with a small, non-encapsulated sclerosing PTC (diameter = 0.8 cm). Regional lymph nodes were not af- fected. The patient’s postoperative course was uneventful, normocalcemia was achieved immedi- ately after parathyroidectomy. Regular check ups have not verified any recurrences or metastases.

The patient has remained free of HPT and thyroid cancer during a follow-up period of 3 years.

Discussion

A higher incidence of certains types of malignancy has been reported in patients with parathyroid ade- nomas. Specifically, an association between primary HPT and PTC has been frequently reported.² In addition, there have been few reports of PTC in patient with secondary HPT,^3–6and its has been sugested that the incidence of malignancy is higher in patients with renal failure than in general population.^7,8Thyroid carcinoma has been reported in patients with renal failure both before and after transplantation.⁹ Frequent reports regarding the copresentation of primary HPT and thyroid carcinoma have prompted speculation of the etiology of this association. However, because primary and secondary HPT are entirely different diseases, the implications of the coassociation between thyroid carcinoma and secondary HPT have been pointed in different etiologic direction, including Figure 1 Follicular variant of papillary thyroid carci-

noma with vesicular nuclei, and hemorrhage in follicular lumens (light microscopy, original magnification·20).

Synchronous papillary thyroid carcinoma and secondary hyperparathyroidism 75

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the incidental detection of occult malignancy at the time of parathyroidectomy.¹⁰

Thyroid cancer was found in 36% of 11 ESRD patients from japan with secondary HPT, compared with 11% in an autopsy control group (p\0.05).³ Various explanations have been proposed for the increased cancer incidence in ESRD. However, the pathogenetic mechanism have not been fully eluci- dated as yet. Several factors directly or indirectly associated with the renal failure and the therapeu- tic regimens applied in the management of these patients may favour malignant transformation and tumor formation. A potential involvement of PTH excess in the enhenced carcinogenesis of these patients has to be discussed. At the cellular level PTH was shown to increase proliferation in the bone marrow and liver in vivo and in T-lymphocytes in vi- tro. In contrast, the active form of vitamin D 1,25- dihydroxycholecalciferol appears to suppress cell proliferation and promote differentiation of imma- ture or neoplastic cells. Hence, the pro-tumor ac- tion of excess PTH may act unopposed due to the deficiency of 1,25-dihydroxycholecalciferol in chronic renal failure contributing to increased tumor formation.¹¹

Immunologic surveillance is generally accepted as a major defense against neoplastic cells, however, uremic patients are considered to be in a state of reduced immunocapacity. Therfore, the incidence of thyroid carcinoma might be high in those patients for this reason.^3,11

Previous neck irradiation, although not present in our patient, appears to increase the risk for thyroid cancer.¹¹In addition, various factors, such as the goitrogenic effects of calcium and excessive production of calcitonine in response to hypercalcemia have been proposed as a common patho- genic mechanism for the coexistence of thyroid carcinoma and HPT. Taylor¹² theorized that calcium carbonate has a goitrogenic effect either by inhibiting the synthesis of thyroxine or by increas- ing iodine clearance by the kidney, and Ellenberg et al.¹³ reported that hypercalcemia also might be carcinogenic.

Since, occult PTC is an occasional incidental finding during surgery for HPT, careful palpation and inspection of the entire thyroid gland at the time of open parathyroid resection is higly recommended.¹⁴

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