Giant intrathyroidal parathyroid adenoma.

Primary hyperparathyroidism (PHPT) is not an uncommon endocrine disorder. However, acute primary hyperparathyroidism, or parathyroid crisis (PC), is a rare clinical entity characterized by life-threatening hypercalcemia of a sudden onset in patients with PHPT. We describe a patient with PC who presented with acute worsening of depressive symptoms, nausea and vomiting, and required emergency surgery. Serum calcium, alkaline phosphatase, and parathyroid hormone were elevated and serum phosphorus was low. An emergency hemithyroidectomy was performed because of none medical control of hypercalcemia. A giant intrathyroidal parathyroid adenoma was diagnosed. PHTP can be a life-threatening situation for patients, requiring immediate surgical treatment. A giant intrathyroidal parathyroid adenoma is an uncommon cause of PC.

INTRODUCTION

Hyperparathyroidism due to parathyroid abnormalities are classified into three forms: primary, secondary, and tertiary. Primary hyperparathyroidism (PHPT) is the third most common endocrine disorder.[1] Parathyroid adenoma accounts for about 85% of all cases of hyperparathyroidism, considering all the forms: primary, secondary and tertiary. Other less prevalent causes include parathyroid hyperplasia (15%) and carcinoma (3-4%).[2] The most common clinical presentation of PHPT is as an asymptomatic disease.[1] However, acute primary hyperparathyroidism, or parathyroid crisis (PC), is rare. Parathyroid crisis is characterized by life-threatening hypercalcemia of a sudden onset in subjects with PHPT. We describe a patient with PC secondary to a giant intrathyroidal parathyroid adenoma who presented with progressive neurological symptoms, nausea and vomiting without medical response to treatment.

CASE REPORT

A 19-year-old female patient was admitted to the orthopedics department for supra-acetabular fibrous dysplasia treatment. She had also been treated for a depression over the past 6 months. The patient did not present any other past medical data of interest. After orthopedic surgery, during the second postoperative day she began to suffer from lethargy, nausea, vomiting, and abdominal pain. Also, the patient reported muscle weakness, fatigue and a worsening of depressive symptoms. A blood analysis was performed which showed elevated Ca2+ (14.2 mg/dL, normal laboratory level 8.8-10.2 mg/dL). The serum phosphorus was low (3.99 ng/mL, normal laboratory level 4.0-19.0 ng/mL) with an increased alkaline phosphatase level (171 UI/L, normal laboratory level 20-90 UI/L). Endocrine evaluation showed elevated parathyroid hormone (PTH) (1207.0 pg/dL, normal laboratory 7-82 pg/dL).

Medical treatment was started with rehydration, forced diuresis and intravenous infusion of biphosphonates. An urgent ultrasonography was requested and showed a 47 × 22 mm nodule in the left thyroid lobe. No other complementary explorations were performed. After two days of intensive medical treatment, the Ca2+ levels had not decreased and the clinical situation of the patient remained similar or even worse. Because of life-threatening hypercalcaemia and a poor response to medical treatment, she directly underwent surgery after a consensus decision between the endocrinologists and the surgeons. A hemithyroidectomy was performed assuming it was an intrathyroiidal adenoma and without time for performing a fine needle aspiration because of the patient's situation. During the surgical procedure, a superior parathyroid gland was observed and not resected. At the end of the hemithyroidectomy, the specimen was open and a clear intra-thyroidal adenoma surrounded by thyroid tissue was observed [Figure 1]. The right thyroid was not touched after this finding. Unfortunately, intraoperative PTH and anathomopathological analyse were avaible but were not used according to the intraoperative findings. On the final anatomopathological examination, an intrathyroidal parathyroid adenoma was found. It had a maximum diameter of 3 cm and the whole specimen weighted 70 g. The postoperative course was uneventful. The patient received doses of Calcium iv during the first day and oral intake began at day two. Oral calcium was then given to the patient in the postoperative period until the fist visit at the outpatient clinic. During follow-up, PTH, phosphorus, and Ca2+ levels normalized. The patient has now recovered properly and continues her standard follow-up.

Figure 1

Image of the thyroid lobe after surgery. Note the giant intrathyroidal nodule that corresponds to the adenoma (3 cm diameter)

DISCUSSION

The prevalence of PHPT is approximately 1:1000. It is also more frequent in older females.[1] The risk of developing this disease increases with a peak incidence between 50 and 60 years, whereas PHPT in children and adolescents is a rare condition.[3] The most common clinical presentation of PHPT is as an asymptomatic disease.[1] However, acute primary hyperparathyroidism or PC, is not frequent. Parathyroid crisis is characterized by life-threatening hypercalcemia of sudden onset in subjects with PHPT. The patient presented with an acute exacerbation of her psychoneurological problems. It has been reported that changes in mental status are characteristic features of hypercalcemic crisis.[45] Moreover, she had muscle weakness. Although neuromuscular manifestations have been described previously, the pathophysiology of these manifestations is not yet clear.[67]

Generally, elective surgery is the most appropriate treatment for PHPT.[8] Moreover, in PC, as a potentially lethal condition, emergent parathyroidectomy has been advocated. Certainly, it has been emphasized that expeditive parathyroidectomy is the cornerstone treatment of patients with PC.[59] There is no clear relationship between surgery and the beginning of toxic, urgent hypercalcaemia.[1]

In surgical series there is an estimated reported prevalence of intrathyroidal parathyroid adenoma that varies from 1.4-6%.[1011] According to embryology, parathyroid glands originate from the third and fourth branchial pouches. After this, the glands caudally migrate to their final positions. Any problems during this migration can lead to the glands settling in an anomalous location, even in the thyroid tissue.[12] In a recent study, localization of most of the adenomas (70.6%) was shown to be on the right side and on the lower third of the thyroid lobes.[13] This study also reported that intrathyroidal parathyroid adenomas were present in 3% of patients submitted for parathyroidectomy.[13] However, reports of a giant intrathyroidal parathyroid adenoma in the literature are exceptional.[14]

It has been noted that the weight of the adenoma correlates with the severity of the PC. Gasparri et al.,[15] found that in a patient with a serum calcium level higher than 15 mg/dL, the mean weight of the removed glands was 4.9 g, whereas it was 2.1 g in patients with serum calcium levels lower than 15 mg/dL. Nevertheless, giant parathyroid adenomas are rare. Lalanne-Mistrih et al.,[16] reported that adenomas heavier than 3.5 g accounted for 7.2% of their series of PHPT.

Differential diagnoses, when very high levels of PTH are present, must be established with parathyroid carcinoma.[17] Parathyroid carcinoma is a rare malignancy with an incidence rate of less than 1% in all patients surgically treated for primary hyperparathyroidism. To the best of our knowledge, only a few cases of intrathyroidal parathyroid carcinoma have been described. The clinical manifestations of hyperparathyroidism in parathyroid carcinoma are usually more severe than in patients with parathyroid adenoma.[14] Fortunately for the patient, the final diagnosis did not show parathyroid carcinoma.

CONCLUSION

Parathyroid crisis is an emergency because high levels of calcium pose a life-threatening situation for patients. Symptoms can be subtle and nonspecific. However, changes in mental status are prevalent, hence, the serum calcium level must be determined in any patient with unexplained central nervous dysfunction. Once the patient with PC has been stabilized, expedited parathyroidectomy must be performed. Finally, giant hyperfunctioning intrathyroidal parathyroid adenoma is a very uncommon cause of PC.