The Changing Face of Primary Hyperparathyroidism.

Primary hyperparathyroidism (PHPT) is a clinical syndrome caused due to inappropriate excessive production of parathormone (PTH) leading to hypercalcemia (occasionally normocalcemia) and hypophosphatemia.

There has been a considerable change in the expression of PHPT over the past eight decades. Initially, there has been an increase and subsequently a decrease in the apparent incidence and prevalence of PHPT in western countries.[1] Yeh et al. later noted that the prevalence of PHPT had tripled after the use of biochemistry autoanalyzers.[2] The clinical spectrum of PHPT has undergone a striking change with asymptomatic form being more prevalent in the developed countries, whereas symptomatic form being more prevalent in the developing countries.

PHPT was classically described as a disease of “stones, bones, abdominal groans and psychic moans.” Nephrolithiasis, osteitis fibrosis cystica, gastrointestinal complaints, and psychological symptoms were prominent manifestations of the disease till two decades ago.

In the current era, manifestations of PHPT are generally mild and often diagnosed incidentally during routine biochemical screening. The incidence of asymptomatic PHPT has been on a rise in the western world. This trend is now being witnessed even in developing countries like India. Data from different studies published from India indicate that the incidence of asymptomatic PHPT is around 5%–38%.[345678910]

In this issue of IJEM, Mallikarjuna et al. have reported the results of their retrospective study on patients with PHPT from South India.[11] In all, 54 patients with a mean age of 48.1 ± 15.8 years were reported to have PHPT. About 39% of these patients were reported to be asymptomatic. This finding seems to be common and is now being increasingly reported from different zones of India. Earlier studies reported prevalence rate of asymptomatic PHPT to be around 5% from India.[5] In our study, we reported prevalence rate of 18% for asymptomatic PHPT.[10] It is evident that over the past decade asymptomatic PHPT is being increasingly reported from India due to frequent screening for calcium levels.

Symptoms of PHPT are reported to be usually mild in developed countries. However, reports from India suggest that symptomatic PHPT still is widely prevalent and severe, especially in public sector hospitals. This may be due to widespread vitamin D deficiency and socioeconomic strata of the population seeking medical aid in public sector hospitals. Mallikarjuna et al. reported 61% of patients to have symptomatic PHPT. In our study, we reported 82% of patients to have some symptoms of PHPT.[10] This indicates a decline in symptomatic PHPT due to early diagnosis.

Musculoskeletal system remains the most common system affected due to PHPT followed by renal and gastrointestinal system.[345678910] Only one study from Kashmir reported renal involvement to be the most common finding in symptomatic PHPT.[9] Neuropsychiatric manifestations of PHPT have been reported to be less frequent. This may be due to the fact that cognitive impairment is difficult to access and often overlaps with non-specific symptoms.

Mallikarjuna et al. reported mean serum calcium level and PTH level to be 12.2 ± 2 mg/dL and 602 ± 721 pg/mL, respectively. PTH levels have been reported to be less in asymptomatic versus symptomatic PHPT. This is consistent with reports from various studies from India including ours. Interestingly, vitamin D deficiency seems to be widely prevalent across India (60%–80%). This has been implicated as one of the reasons for increasing prevalence of symptomatic PHPT. However, there was no correlation between vitamin D levels and symptoms of PHPT.[10]

The advent of newer imaging technology has led to better preoperative localization and enabled us to offer the patient minimal invasive surgery for PHPT. Ultrasonography (USG) and PTH sestamibi scan remain the best cost-effective imaging modalities for preoperative localization. The current study by Mallikarjuna et al. reported sensitivity of USG and PTH sestamibi to be 72% and 71%, respectively. This is lower than most other studies reported from India.[1213] This suggest that eyes of an experienced, well-trained sonologist will detect the culprit parathyroid gland in most cases. This is important in a resource-limited country like ours where PTH sestamibi scan facilities may not be easily available.

In our quest to offer minimally invasive surgery to patients with PHPT, we aim to localize the culprit parathyroid gland preoperatively. There remains a subset of patients where preoperative imaging is not able to localize the culprit parathyroid gland. In such cases, newer positron emission tomography (PET) radiopharmaceutical tracers are being increasingly used. 11C methionine or 18Flurocholine-based PET scan seems to have greater sensitivity and diagnostic performance in PHPT cases where sestamibi scan or USG are negative.[14] Four-dimensional computed tomography provides excellent anatomic detail for preoperative localization in eutopic and ectopic locations, while multiple phases show uptake characteristics that help differentiate parathyroid lesions from lymph nodes and thyroid nodules.[15]

Surgery remains the main choice of treatment for most patients of PHPT. In August 2014, the National Institute of Health published revised guidelines for the management of asymptomatic PHPT.[16] Surgery was considered the best treatment options for those with end-organ damage with longer life expectancy based on clinical data. Neuropsychiatric manifestations were not included in the guidelines because of inconsistent nature of these symptoms, lack of data, and failure of symptoms to reverse following parathyroidectomy. Medical management with calcium sensing receptor agonist cinacalcet is advised for elderly with comorbidities who are unfit for surgery.

The results of the present study indicate that the incidence of asymptomatic PHPT is increasing even in India. The increasing awareness and widespread use of multichannel biochemistry autoanalyzer has led to earlier detection of PHPT in course of the disease. Symptoms, if any, are usually mild nowadays and far away from the classically described ones. Newer and better imaging modalities have increased the preoperative localization of parathyroid adenoma enabling us to offer minimally invasive surgery. Routine estimation of serum calcium in our patients is worthwhile!