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Parathyroid adenoma apoplexy as a temporary solution of primary hyperparathyroidism: a case report
© Pereira et al; licensee BioMed Central Ltd. 2007
Received: 14 February 2007
Accepted: 17 November 2007
Published: 17 November 2007
The natural history of patients with spontaneous parathyroid necrosis is unknown. In this case report we describe the clinical course, laboratory, radiographic, bone densitometry tests, parathyroid ultrasonography and scintigraphy examinations of a patient performed over a period of eight years after she first presented with a sudden episode of spontaneous resolution of primary hyperparathyroidism (PHPT).
A 24-year-old woman with a clinical history and laboratory and radiographic tests compatible with PHPT suffered a sudden episode of cervical pain and presented with clinical evidence of hypocalcemia. Biopsy of a cervical nodule revealed necrotic material compatible with ischemia of the parathyroid. The follow-up of the patient presented four distinct phases: the first, which lasted two years, was compatible with a period of bone hunger during which it was necessary to introduce calcitriol and calcium carbonate. During this period, the patient showed bone mass gain. The second phase was characterized by normalization of calcium and parathyroid hormone levels and its end was difficult to define. During the third phase there was a recurrence of hypercalcemia associated with elevated parathyroid hormone (PTH) levels and loss of bone mass. The last phase corresponded to the interval after parathyroidectomy, which was characterized by normalization of serum levels of calcium and PTH, as well as bone mass gain.
This case report indicates that spontaneous resolution of PHPT by adenoma necrosis is potentially temporary. Thus, in cases in which a conservative approach is chosen, clinical and laboratory follow-up is indispensable. Bone mass measurement is a useful tool in the follow-up of these cases. However, this option exposes the patient to a potential roller-coaster ride of bone mass gain and loss, whose long term consequences are still unknown.
Although the natural history of primary hyperparathyroidism (PHPT) is incompletely understood, in many cases the calcium level remains stable when monitored on a regular basis [1, 2]. In parallel, over the last two decades the number of reported cases that do not follow this pattern has increased . The first case of cyclic PHPT was recently reported  and sporadic cases of spontaneous resolution due to apoplexy of parathyroid adenomas have been reported more frequently [3, 5, 6]. In the latter situation most patients were submitted to early surgery or were followed for as long as 30 months but this did not include bone mass evaluation.
In this case study we report the details of a patient who presented with spontaneous remission of PHPT and was followed for eight years after the apoplexy episode, at which time she presented with recurrence of hypercalcemia. In this case, in addition to obtaining clinical and laboratory documentation, the authors prospectively evaluated the patient's bone densitometry.
Laboratory work-up upon patient admission
Ionized calcium (mmol/L)
0.8 (0.7 – 1.7)
1.5 (0.4 – 4.0)
2.0 (0.3 – 13)
14.0 (13 – 30)
Plasma cortisol (μg/dl)
6.4 (5.0 – 20.0)
25-Hydroxyvitamin D (ng/ml)
11.0 (15.0 – 80.0)
210 (15.0 – 60.0)
Parathyroid scintigraphy with sestamibi in 2003 and before surgery did not show abnormal uptake of the radiopharmaceutical. Ultrasound showed a reduction of the nodule only in 2006, when its size was 0.53 cm3.
Bone mineral densitometry (BMD) was obtained using two different instruments. In 2000 and 2001, the patient showed bone mass gain in lumbar spine (3.3%) and femoral neck (7.4%), (Figure 2C). These examinations were performed with a Sophos L-XRA instrument (Sophos, Paris, France), which did not include software for the forearm. Starting in 2003, the examinations were performed with Hologic instruments (4500 W, Waltham, MA, USA, QDR System Software Version 11.2). In 2003 and 2006 BMD was: a) L1–L4 = 0.846 and 0.787 g/cm2; b) total hip = 0.984 and 0.914 g/cm2 and c) 1/3 distal radius = 0.475 and 0.423, respectively (Figure 2C).
The preoperative results obtained for the patient were as follows: total calcium= 10.7 mg/dl, Ca++ = 1.38 mmol/L, phosphorus = 3.1 mg/dl, ALP = 186 U/L, and PTH = 73 pg/ml.
In view of the current status of primary hyperparathyroidism as a frequent disease that is usually asymptomatic, a challenge regarding the management of patients with this disease is to identify the best treatment option, considering that surgery is the only curative option .
After almost two decades of surveillance of patients in a chronic PHPT state, it is necessary to point out other aspects that used to be imperceptible and/or rare and that today represent new challenges regarding the treatment of these patients. Patients with PHPT presenting with normal serum PTH levels have been occasionally reported . However, because of its frequency, the occurrence of spontaneous PHPT resolution by apoplexy of parathyroid adenomas is even more important. Onoda et al.  in 1994 stated that only 25 such cases had been reported. However, the frequency of this problem has increased and at least 26 additional similar cases have been reported since that time . These patients either submitted to surgery early [5, 6], or were followed for about 3 years, and there is no information about a natural evolution monitored over a more prolonged time with ultrasonographic and scintigraphic evaluation. In particular, none of these studies reported the evolution of BMD in these patients. In this case report we describe the evolution of all of these parameters over a period of 8 years in a patient who presented with spontaneous remission of PHPT followed by recurrence of the functional disorder at the end of this 8 year period. Based on this case, it is possible to extract important information regarding appropriate clinical and surgical conduct and the most appropriate timing for surgery.
The first aspect to be emphasized in this case is that punch biopsy of the parathyroid, at the time of adenoma infarction, associated with anatomopathologic examination after parathyroidectomy of the same gland, showed evidence of previous necrosis and benign proliferation of parathyroid cells indicating recurrence of parathyroid adenoma.
The first phase, which followed the infarction of the parathyroid adenoma, is compatible with a state of bone hunger, which is expected in patients with the important bone disorder of PHPT, as demonstrated in the present case by the elevation of alkaline phosphatase and the clearly visible radiologic changes of PHPT. During this period PTH remained elevated as a physiological adaptation to the increased calcium utilization by bone and bone mass recomposition. However, the periods of apparent normalization of parathyroid functioning that follow this phase and the later recrudescence of PHPT are difficult to delimit. This is largely due to the fluctuation of serum calcium and PTH levels that may occur in these patients. The undefined signs and symptoms may produce an undesirable loss of bone mass and non-quantifiable changes in bone quality that may not be fully corrected after definitive surgery. This aspect should be particularly considered in order to define the most appropriate therapeutic course. In this reported case, measurement of bone mass proved to be a sensitive and objective procedure for the demonstration of disease activity and was useful regarding the decision about the need for surgery.
Currently, different centers are performing parathyroid surgery by minimally invasive procedures (MIP) with huge success, thus providing a less traumatic and attractive alternative therapy for PHPT [10, 11]. The standardization of these procedures and of the examinations that usually are associated with these procedures, such as optimizing parameters of parathyroid localization (intraoperative scintigraphic scan) and to assure surgical success (intraoperative determination of quick PTH) will allow the use of these therapeutic options on a large scale . However, in relation to the patient described herein there are some concerns about doing a MIP: a) the patient had a negative scan with sestamibi, b) the possible presence of more than one parathyroid nodule and c) the previous parathyroid apoplexy could result in morphological alterations secondary to hemorrhage. It was considered that this patient should be included in the group for which conventional surgery would be more appropriate. According to Micolli et al., (2000)  approximately 30% of the patients with PHPT are suitable for conventional surgery.
This case indicates that the apparent cure that follows necrosis of a parathyroid adenoma is potentially temporary. All data suggest that an early surgical approach is acceptable for these patients. Conservative management, which involves periodic clinical and laboratory examinations, definitely results in higher costs. Our data also suggest that in addition to calcium and PTH measurements, bone densitometry is a most useful tool for the follow up of these patients.
Written informed consent was obtained from the patient for publication of this case report.
Study supported by FAEPA. (Fundação de Apoio ao Ensino, Pesquisa e Assistência do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo)
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