Abstract
Parathyroid lipohyperplasia is an extremely rare cause of hyperparathyroidism. According to a MEDLINE search, there have been only 9 previously reported cases of parathyroid lipohyperplasia in the English-language literature. We report a new case of parathyroid lipohyperplasia, with a brief discussion of this rare disease process.
Introduction
Parathyroid hyperplasia is a cause of hyperparathyroidism defined as a proliferation of parenchymal cells leading to an increase in gland weight. 1 This increase in weight is a result (at least in part) of the glands’ high adipose tissue content. The two most common types of parathyroid hyperplasia are chief cell hyperplasia and water-clear cell hyperplasia. Only 9 cases of parathyroid lipohyperplasia previously have been reported in the English literature.2–4
Case report
A 60-year-old woman was referred to our clinic with a 1-year history of recurrent kidney stones; one episode had been complicated by urosepsis. She had experienced multiple urinary tract infections during this time. Her medical history was significant for a 3-year history of hypothyroidism treated with levothyroxine (L-thyroxine), and her current thyroid-stimulating hormone level was 6.24 mIU/L (normal 0.30 to 3.0).
Preoperative laboratory studies revealed a parathyroid hormone (PTH) level of 26.8 pg/ml (normal 15 to 65) with a serum calcium level of 11.3 mg/dl (normal 8.9 to 10.1). The patients PTH had been as high as 65 pg/ml with a calcium level at that time of 9.4 mg/dl. Twenty-four-hour urine calcium was normal at 210 mg/24 hours. Computed tomography of the abdomen revealed persistent bilateral nephrolithiasis, and a bone density scan showed well-preserved bone mass. Sestamibi scanning was significant for a subtle mismatch of the dual isotope images corresponding to the inferior right pole of the thyroid. Further imaging by ultrasonography showed two discrete nodules in the left thyroid—one measuring 6 mm and the other, which was cystic, measuring 4 mm. There was no evidence of parathyroid adenoma.
The patient underwent four-gland parathyroid exploration with resection of three and a half parathyroid glands. After resection, the patient's intraoperative PTH levels fell from a baseline of 144 pg/ml to 15 pg/ml at 5 minutes, and to 13.9 pg/ml by 15 minutes. Postoperatively, the patient's calcium level ranged from 7.6 to 8.7 mg/dl.
The resected specimens consisted of tissue from all four parathyroid glands; all were enlarged. In comparison to a normal parathyroid gland (figure, A), the glands showed an admixture of predominantly mature adipose tissue in addition to normal parathyroid stroma (figure, B). The glands’ weight and composition were as follows:
Figure. A: Image shows a normal parathyroid gland. B: The patient's resected left inferior parathyroid gland weighs 235 g. It is comprised of 70% adipose tissue, consistent with lipohyperplasia. Its remaining stromal component consists of 100% chief cells (H&E, original magnification x40).
The left inferior parathyroid weighed 235 mg; 70% adipose (normal 40 to 65 mg and up to 30% adipose).
The right inferior gland was 209 mg; 70% adipose.
The left superior gland weighed 80 mg; 40% adipose.
Half of the right superior gland weighed 64 mg; 70% adipose.
Four days postoperatively, the patients calcium levels normalized to 9.3 to 9.9 mg/dl, and her PTH level fell to 4.57 pg/ml.
Discussion
Straus et al first described lipohyperplasia as a 50% fat/50% parenchymal pattern of normal mature parathyroid tissue and glands that were on average five times the weight of normal parathyroid glands. 2 The difference between lipohyperplasia and other types of parathyroid hyperplasia is that the increase in size is due to lipomatous tissue and not other stromal components.
Histologically, glands affected by lipohyperplasia are similar in appearance to lipoadenomas and demonstrate an increase in both stromal fat and parenchyma. 4 Despite this histologic similarity, lipohyperplasia differs from lipoadenoma in that lipohyperplasia is present in all four glands. Parathyroid glands with lipohyperplasia may be confused histologically with hamartomas. However, hamartomas have a complex organoid parenchymal pattern with a mixture of parathyroid cell types.5,6
The clinical presentation of hyperparathyroidism caused by lipohyperplasia is similar when caused by parathyroid hyperplasia. A review of the previous 9 cases of lipohyperplasia shows that clinical symptoms were noted in 67% of the cases; the mean calcium level was 12.46 mg/dl, and the mean PTH level was elevated 86% of the time. The mean age was 52.4 years, with a female predilection of 3.5:1. The most common presenting symptom was fatigue (66%), and other reported findings were bone/joint pain, nocturia, depression, memory loss, constipation, signs of cardiovascular disease, and nonspecific ECG changes. 4
Parathyroid lipohyperplasia may be difficult to identify by sestamibi scan because there is multi-gland involvement, high adipose content, and relatively small size compared to parathyroid adenomas. Seethala et al performed sestamibi scanning for confirmed cases of lipohyperplasia. In this series of 3 patients, only one had incomplete washout, suggesting four-gland hyperplasia. 4 Similarly, our patient had a sestamibi scan that did not suggest four-gland hyperplasia; only a subtle mismatch near the right inferior pole of the thyroid was observed. Historically, ultrasonography has been shown to increase the sensitivity of sestamibi to approximately 90% for identifying parathyroid hyperplasia, 7 but it was not helpful in suggesting abnormal glands in this case.
Histology, PTH levels, and a radioguided gamma probe may serve as helpful intraoperative adjuncts to locate pathologic parathyroid glands. Lipohyperplasia can be diagnosed by frozen section, but this may prove difficult because parathyroid specimens may be seen as normal parathyroid tissue or only adipose tissue. This method is enhanced by measuring and weighing resected specimens to identify large and most likely pathologic specimens.
Monitoring intraoperative PTH for appropriate decline (>50%) after excision is crucial for confirmation that the pathologic tissue has been removed. 2 In cases in which there is a localizing sestamibi or ultrasound scan and PTH falls by 50% after unilateral exploration and removal of a parathyroid gland, surgery may be concluded. 7
In the last decade, intraoperative radioguided resection has been popularized. One larger study examining radioguided gland resection in 92 patients with parathyroid hyperplasia reported a 100% success rate in localizing the hyperfunctional parathyroid glands. 8
In the case of parathyroid lipohyperplasia, when there are nonlocalizing preoperative studies, a thorough four-gland exploration should allowthe surgeon encountering this rare entity to treat it appropriately. It is presently unknown if intraoperative gamma probing would have been a significant help with the present case, but it is often helpful with nonlocalizing multi-gland disease.
No cases of gross recurrence of lipohyperplasia or lipoadenoma have been reported, and there has been only 1 case of recurrent hypercalcemia after subtotal parathyroidectomy.4,9 Despite its rarity, with proper surgical excision one can expect a successful outcome in these cases.
Footnotes
Acknowledgment
Our thanks to Dr. Thomas Colby of the Department of Pathology at the Mayo Clinic for interpreting and providing the pathology images for this article.