The most common presentation of PHPT is asymptomatic hypercalcaemia with routine biochemical screening. However, symptomatic disease is more common in resource-limited countries.
Normocalcaemic PHPT is another variant of PHPT, is diagnosed in the context of nephrolithiasis or metabolic bone disease and is characterized by normal serum calcium levels when measured at least twice over 6 months despite elevated PTH levels after excluding the causes for secondary hyperparathyroidism [4].
The important factors determining the presentation of disease are the availability of routine biochemical screening, the prevalence of vitamin D deficiency, screening for PHPT with a diagnosis of osteoporosis or osteopenia and awareness among clinicians regarding the manifestations of disease.
Although the incidence of target organ damage has greatly decreased in the modern era, classical manifestations of PHPT are still present in our country setting, where universal biochemical screening of PHPT is not available.
A lack of awareness among clinicians regarding the various manifestations of the disease also leads to delayed diagnosis. Furthermore, delayed medical attention of the patient also contributes to delayed diagnosis. Our patient was evaluated for 2 months by a general practitioner after delayed medical attention for 3 months. During that time, specific investigations were not conducted and only managed symptomatically. Later, she was admitted to the orthopedic discipline with a vertebral fracture. Initially, she was evaluated for tuberculosis, hematological malignancies and rheumatic disorders, which are common in our country. Unfortunately calcium evaluation was not performed at initial presentation. A few weeks later, PHPT was identified as having a hidden etiology for the vertebral fragility fracture through serum calcium and further investigations. However, PHPT should be suspected quickly in a young patient presenting with fracture or bone lesions and serum calcium evaluation should be performed as soon as possible. Therefore, clinicians must be aware of the spectrum of manifestations of PHPT for prompt diagnosis without delay to prevent progression and to avoid unnecessary evaluation.
Bone disease and kidney stones are classical target organs affected in PHPT. Back pain is one of the most frequent symptom in general practice that can lead patients to consult various specialties, including general practitioners, rheumatologists, orthopedists and neurosurgeons. Therefore, interdisciplinary collaboration is necessary in this situation.
The classic imaging appearance is osteitis fibrosa cystica (OFC), which is relatively rare today. OFC is characterized by bone pain clinically and subperiosteal bone resorption on the radial aspect of the middle phalanges, tapering of the distal clavicle, a salt and pepper skull appearance, bone cysts and brown tumors of long bones radio graphically. Parathyroidectomy results in complete regression of brown tumors in most patients [5].
Decreased BMD is a well-recognized skeletal manifestation of PHPT. PHPT preferentially affects the peripheral skeleton rather than the axial skeleton. On the other hand, postmenopausal osteoporosis tends to affect the axial skeleton more prominently. Therefore, BMD should be measured at the lumbar spine, hip and distal third of the forearm in the evaluation of PHPT.
A recent population-based study revealed that patients with PHPT had an increased overall risk of fractures including fractures of the vertebrae, distal forearm and the pelvis, with a mild increase in the risk of femoral fractures. These findings indicate that PHPT has an impact on cancellous bone in addition to cortical bone. All of the above bone manifestations can be prevented if early diagnosis of PHPT is warranted [6].
MEN and other hereditary syndromes associated with PHPT should be considered when evaluating young patients with PHPT [7]. However, we excluded hereditary associations in our patient with a personal and family history and a with normal pituitary hormone profile because of poor resources for genetic testing.
After the biochemical diagnosis of PHPT, preoperative localization studies help with planning a minimally invasive approach for patients with single-gland disease. Approximately 80% of patients have a single parathyroid adenoma, 10% have more than one adenoma, another 10% have hyperplasia in 4 glands, and less than 1% of patients have parathyroid carcinoma. Multiple imaging modalities are available for localization. Commonly utilized first-line imaging methods include ultrasonication, technetium-99 m sestamibi scanning and 4D-CT scanning [8].
Symptomatic patients with PHPT should undergo parathyroid surgery because it cures the disease, improves BMD, decreases fracture risk and decreases the formation of renal stones. However, there are proposed criteria by a fourth international workshop on PHPT for asymptomatic patients to proceed with surgery, as most of them do not have disease progression. Surgery is recommended for asymptomatic patients for whom one or more of the following conditions are present [9].
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Age younger than 50 years.
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Serum calcium greater than 1 mg/dL above the upper limit of normal.
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A T-score greater than − 2.5 was given at the lumbar spine, total hip, femoral neck or distal 1/3 of the radius.
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Vertebral fracture on imaging.
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eGFR < 60 mL/min/1.73 m2.
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Twenty-four-hour urinary calcium > 400 mg/day.
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Presence of nephrolithiasis or nephrocalcinosis on imaging.
The rapid intraoperative PTH assay method is useful for confirming the successful removal of adenoma. It takes advantage of the short half-life (three to five minutes) of PTH. In Sri Lanka, the “>50% reduction criterion” is commonly used to assess success [10]. A “Cure” in PHPT can be established when normocalcaemia lasts at least 6 months after surgery [11].
Postoperative hypocalcaemia can occur due to hypoparathyroidism or hungry bone syndrome (HBS). HBS is caused by the massive transfer of calcium into bone tissue and is associated with rapid, severe and prolonged hypocalcaemia, hypophosphatemia and hypomagnesemia. High PTH levels, large parathyroid adenoma, severe hypercalcaemia, the presence of bone disease and vitamin D deficiency are risk factors for HBS. Treatment requires very high doses of calcium and active vitamin D supplements. High-risk patients should be monitored carefully during the postoperative period for the development of HBS [12].
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