Abstract
Summary
Primary hyperparathyroidism most commonly presents with hypercalcaemia. Rarely, parathyroid apoplexy or haemorrhage mimicking a thyroid bleeding cyst is the first presentation of a parathyroid adenoma. A woman presented with a sudden-onset painful ‘goitre’. Ultrasound showed a cystic nodule located posterior to rather than in the right thyroid lobe, suggesting parathyroid adenoma bleeding. Biochemistry showed mild primary hyperparathyroidism. 99mTc-pertechnetate/sestamibi showed no uptake in the nodule, which was interpreted as a cold thyroid nodule. 18F-fluorocholine PET/CT showed uptake in the nodule, suggestive of a parathyroid adenoma. Persistent mild primary hyperparathyroidism complicated by nephrolithiasis and osteopenia favoured parathyroidectomy over a wait-and-see approach. The patient was referred for parathyroidectomy along with right thyroid lobectomy. Pathology showed an adenoma, with an eccentrically located cystic structure filled with red blood cells surrounded by a thickened fibrous capsule. In conclusion, cervical pain/haemorrhage with hypercalcaemia points to the diagnosis of parathyroid apoplexy, mimicking a thyroid bleeding cyst. Workup with ultrasound and, if available, 18F-choline PET/CT allows for timely surgery, minimizing the risk of recurrent and severe bleeding.
Learning points
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A bleeding cyst may be located posterior to rather than in the thyroid, suggesting a parathyroid haemorrhage.
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Neck pain and/or haemorrhage along with primary hyperparathyroidism point to parathyroid apoplexy.
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A two-step presentation has been described, with a first phase of local symptoms to be followed by visible and possibly life-threatening compressing bleeding.
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Therefore, an expedited workup is needed, allowing for timely surgery.
Background
Diagnostic workup includes dedicated ultrasonography to clear the suspicion of a parathyroid adenoma haemorrhage and to discern it from thyroid nodule haemorrhage. A negative 99mTc-pertechnetate/sestamibi scan has been reported in most cases of parathyroid apoplexy. Scarce blood supply as well as replacement of metabolically active cells by haemorrhage may contribute to the absence of sestamibi uptake. To our knowledge, this is the first parathyroid adenoma apoplexy case in which 18F-choline PET/CT has been performed.
Case presentation
A 55-year-old woman presented to the ear, nose, throat/head and neck surgery department with a sudden-onset painful goitre. In the family history, we noted thyroid surgery. Besides right-sided neck pain, intermittent limited dysphonia was present. The ultrasound report read a sharply defined hypoechogenic nodule in the right thyroid lobe measuring 24.1 mm × 17.8 mm × 18.2 mm. No enlarged lymph nodes were noted. The patient was referred to the endocrinology department for fine needle aspiration (FNA). Repeat ultrasound showed a partially cystic nodule located posterior to rather than in the right thyroid lobe, suggesting parathyroid adenoma bleeding rather than thyroid nodule bleeding (Fig. 1A and B). FNA was deferred. Biochemistry showed mild hypercalcaemia 2.53 mmol/L (normal range (NR): 2.15–2.5), elevated PTH 146 ng/L (NR: 15–65) and fractional calcium excretion 0.015 (>0.02 being regarded as evidence of primary hyperparathyroidism and values between 0.015 and 0.02 as highly suggestive of primary hyperparathyroidism), and serum phosphate was 0.66 mmol/L (NR: 0.81–1.45) and 25-OH vitamin D was 22.8 g/L, all suggesting primary hyperparathyroidism. The 24-h urine calcium secretion was 5.3 mmol/24 h (NR: 2.5–7.5). Looking further, we obtained a calcium–phosphate ratio of 3.83 (2.53/0.66), which was above the diagnostic threshold for primary hyperparathyroidism of 2.55 and even above the median value of 3.32 in a large series of primary hyperparathyroidism (1). Hyperparathyroidism persisted over a period of 64 days (from the day of the first blood sample until the day of surgery). Bone mineral density showed osteopenia (T-score: lumbar vertebral column 0.3, femoral neck −1.6, whole hip −0.3, radius −0.5) (WHO criteria for T-score: ≥−1.0 normal bone density, <1.0 and ≥−2.5 osteopenia, <−2.5 osteoporosis), and ultrasound of the kidneys showed multiple kidney stones, indicating primary hyperparathyroidism necessitating surgery.
Ultrasound at presentation, axial section (A), showing a partially cystic nodule located posterior to or in the right thyroid lobe. Ultrasound 1 month after presentation, axial section (B), showing a predominantly solid nodule. Coronal section of the 18F-choline PET/CT showing a distinct parathyroid adenoma at the right side (C).
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 4; 10.1530/EDM-22-0385
99mTc-pertechnetate/sestamibi 1 month after the initial presentation showed no uptake in the nodule, which was interpreted as a cold thyroid nodule. 18F-fluorocholine PET/CT 2 months after presentation showed uptake in the nodule, suggestive of a parathyroid adenoma, thereby supporting the working hypothesis (Fig. 1C). The patient was referred for parathyroidectomy along with right thyroid lobectomy in case of thyroid adhesion. Preoperatively, the right superior parathyroid had a normal appearance. Because the 18F-fluorocholine PET-CT had suggested an upper parathyroid location, the right upper parathyroid was nevertheless resected and sent for frozen section. The right inferior parathyroid was strongly fused with the thyroid as well as with the surrounding strap muscles. Therefore, the surgeon decided to perform a right hemithyroidectomy. PTH was 146 ng/L (NR: 15–65 ng/L) at induction and decreased to 14 ng/L 1 h postoperatively. Figure 2 shows a timeline with procedures, calcium and PTH concentrations. Pathology showed a parathyroid adenoma, approximately 17 mm in diameter, with an eccentrically located cystic structure (5–6 mm in diameter), filled with red blood cells and surrounded by a thickened fibrous capsule. The cyst wall contained numerous macrophages with iron pigment deposition (Fig. 3). Postoperative recovery was uneventful and cure of primary hyperparathyroidism was confirmed at follow-up at 1 month.
Timeline with procedures, calcium and PTH concentrations. The grey bars represent the reference values for PTH (ng/L) and calcium (mmol/L). Blue dots represent the measurements in the case presented. After removal of the parathyroid adenoma and the adherent right thyroid lobe an immediate drop of PTH was observed with PTH values of 14 and 5 ng/L, 10 min and 1 h after resection, respectively.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 4; 10.1530/EDM-22-0385
H&E staining. Parathyroid adenoma on the left with cyst (arrow) filled with red blood cells and accumulation of macrophages in the cyst wall. Normal thyroid tissue on the right.
Citation: Endocrinology, Diabetes & Metabolism Case Reports 2023, 4; 10.1530/EDM-22-0385
Discussion
Primary hyperparathyroidism most commonly presents with hypercalcaemia. Rarely, parathyroid apoplexy or haemorrhage is the first presentation of a parathyroid adenoma, as it was in the case presented here. The combination of neck haematoma and primary hyperparathyroidism may point to the diagnosis of parathyroid apoplexy. Nylen et al. (2) proposed a classification of parathyroid apoplexy according to the extent of haemorrhage and clinical presentation. Our case fits within type II with sudden pain located in the neck, without visible haematoma formation. In conclusion, although hypercalcaemia is quite common, due to apoplexy or haemorhage remission of the hyperparathyroidism, subsequent normalisation of calcaemia or even hypocalcaemia may occur (3, 4).
Clinical presentation may vary markedly. In some patients, like in ours, pain without obvious bleeding may be present, with spontaneous resolution of pain and regression of bleeding as demonstrated by sequential ultrasound. Other patients may present with obvious and life-threatening bleeding. Severity may also increase over time due to recurrent bleeding. A two-step presentation has been described with a first phase of local symptoms followed by a recovery period to be followed later by visible and possibly threatening compressive haemorrhage (5, 6). Therefore, some authors advocate surgical treatment within 1 month of presentation, to avoid the risk of recurrent and potentially more severe bleeding (3). Clinical signs indicating urgent surgery are acute anaemia, hypotension, a hypercalcaemic crisis or airway compression (7, 8).
Diagnostic workup includes dedicated ultrasonography to clear the suspicion of a parathyroid adenoma haemorrhage and to discern it from a thyroid nodule haemorrhage. Negative 99mTc-pertechnetate/sestamibi scan has been reported in most cases of parathyroid apoplexy (3, 6, 7), as it was in the patient presented here. Scarce blood supply as well as replacement of metabolically active cells by haemorrhage may contribute to the absence of sestamibi uptake. To our knowledge, this is the first parathyroid adenoma apoplexy case in which 18F-choline PET/CT has been performed. 18F-choline uptake in the nodule supported the diagnosis of parathyroid adenoma bleeding and allowed for a precise surgical plan. The discrepancy between (negative) sestamibi SPECT and (positive) choline PET is often observed (9), but in this particular case, healing of the haemorrhage occurring in the time lapsed between the two examinations may have contributed to the discrepancy. Adherence of parathyroid adenoma haemorrhage to the thyroid, necessitating parathyroidectomy and thyroid lobectomy, was seen in our patient as well as in other patients reported (5). The reasons for preferring surgical intervention to a wait-and-see attitude here concern residual hyperparathyroidism in a young lady, complicated by nephrolithiasis and osteopenia (10), and the previously described two-step phenomenon in which severe bleeding was described.
In conclusion, cervical pain/haemorrhage along with hypercalcaemia point to the diagnosis of parathyroid apoplexy. Expedite workup with ultrasound and, if available, 18F-choline-PET/CT allows for timely surgery, minimizing the risk of recurrent and more severe bleeding.
Declaration of interest
The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the case study reported.
Funding
This study did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.
Patient consent
Written informed consent for publication of their clinical details and clinical images was obtained from the patient.
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