The diagnosis of primary hyperparathyroidism (pHPT) is based on the finding of normal/high blood calcium levels associated to inadequately high/normal parathyroid hormone (PTH) circulating levels. The majority of cases of pHPT are currently represented by asymptomatic/paucisymptomatic forms of the disease, with little or no progression. Moreover, pHPT is characterized by recurrent kidney stones and osteoporosis, disorders frequently observed in the normal population, independently from parathyroid diseases. Surgery is indicated in cases of symptomatic pHPT, while in mild forms of the disease a conservative approach may be chosen.
Imaging localization of enlarged parathyroid glands is used in the preoperative detection and spatial assessment of a pathologic parathyroid glands. When clinical and biochemical results do not fully support the diagnosis of pHPT, imaging studies may lead to false diagnosis.
In the present report we describe the clinical history of two patients suspected to be affected by pHPT, whose imaging data were superimposable, but final diagnosis was different.
A 63-year-old woman was referred to the Mineral Metabolic Unit by her family doctor with a history of recurrent kidney stones and persistent pHPT, having previously undergone surgery on the basis of clinical and imaging findings suggesting the presence of a parathyroid adenoma. In the past history of the patient, diagnosis of normocalcemic symptomatic pHPT was made by her family doctor, which requested a scintigraphy with 99Tc-MIBI and a neck-thoracic CT. Biohumoral data showed elevated circulating PTH levels (88 pg/ml; N.V. = 10-70 pg/ml), normal blood total calcium (9.2 mg/dl; N.V. = 8.8-10.4 mg/dl) and increased urine calcium excretion (385 mg/die; N.V. = 100-300 mg/die). Hip and lumbar bone densities showed the presence of osteoporosis (neck BMD: T-score -2.5, lumbar BMD: T-score = -2.7); a previous exam (5 years earlier) showed the presence of osteopenia (lumbar T-score = -2.2).
The scintigraphy showed a large mediastinic non homogenous area of uptake visualized also in delayed (2 hours) images (Fig. 1b), suspecting the presence of pathologic parathyroid tissue. CT-scan confirmed the presence of a conspicuous mass (diameter 4x5x5 cm) in the mediastinum, with the upper extremity contiguous to the inferior pole of the right lobe of the thyroid gland (Fig. 1c). Post-contrastographic enhancement was very poor. Without hypotheses on the nature of the mass its localization well-matched with a pathologic ectopic parathyroid gland.
Figure 1 – Patient 1: sarcoidotic lymph node. A) Ultrasound: at the infrajugular right parasagittal site is present a scarcely echoic, huge mass with sharp edges. B) 99TcMIBI Scintigraphy: image obtained 90 min after injection of the tracer; a “hot” spot is shown in the upper mediastinum-low neck. C) Computed tomography: on the right side of esophagus and trachea, a scarcely contrast- enhanced mass is present.
The patient underwent surgery for removal of the suspected parathyroid adenoma. At surgery, no evidence of pathologic PT gland(s) could be found and histopathology of the mass showed evidence of sarcoid lymphonodal mass, with persistent pHPT after surgery.
During a recent ultrasound (US) kidney evaluation, the radiologist examined the neck, where a large nodular lesion was found caudally to the inferior pole of the right lobe of the thyroid, extending into the anterior mediastinum, and its parathyroid origin was suggested (Fig. 1a).
A careful clinical evaluation led to the following data. The patient had no family history of kidney stones, osteoporosis, fractures or other related diseases. She underwent menopause when she was 54 year-old. A vague abdominal pain and depression were present for many years. The patient never complained of respiratory symptoms. She was not assuming any chronic medical therapy.
Biohumoral data showed absence of activation of the indexes of bone turnover. Routine blood and urine testing and creatinine clearance were in the normal range. Measurement of blood and urine calcium on three different days on a diet containing 1 gr/day of calcium and 100 mEq/day of sodium, showed serum levels of ionized calcium in the normal range (4.5-4.7 mg/dl, N.V. = 4.2-5.3), total serum calcium in the low-normal range (8.7-9.2 mg/dl) and urinary calcium higher than normal (380-500 mg/day). Serum phosphorus levels were 3.5 mg/dl (N.V. = 2.5-4.5) with normal total serum protein (7.0 mg/dl; N.V. = 6-8) and modestly elevated circulating PTH levels (70-90 pg/ml). Both 25(OH) vitamin D and 1,25(OH)2 vitamin D levels were in the normal range (respectively 22 ng/ml; N.V. = 12-55 ng/ml and 42 pg/ml; N.V. = 20-70 pg/ml). Urinary oxalate levels were normal.
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Therefore, the results of the biohumoral exams did not confirm the suspect of pHPT, and primary hypercalciuria was considered the most likely cause of kidney stones, with increased bone loss and secondary hyperparathyroidism. Indeed, the presence of a mixed, absorptive and renal hypercalciuria was confirmed in this patient by specific testing and PTH circulating levels returned to normal after four months of appropriate medical therapy and dietary intervention.