Protean Presentations of Parathyroid Adenoma in Childhood.

Parathyroid adenoma is a rare disease which is known to present with protean manifestations, leading to misdiagnosis in the initial stage of the disease. It is known to pose a diagnostic dilemma to the clinician, in which a high index of suspicion alone often leads to a proper diagnosis and timely management. We encountered two such cases who presented to us with varied presentation, in which nuclear scintigraphy along with intraoperative parathyroid hormone assay played a major role in diagnosis and management.

INTRODUCTION

Primary hyperparathyroidism is rare in children, occurs in 2–5/100,000 children,[1] and may be due to parathyroid adenoma, familial hyperparathyroidism associated with multiple endocrine neoplasia or secondary to malignancy. Primary hyperparathyroidism is known to present with protean manifestations, leading to misdiagnosis in the initial stage of the disease. Adenoma is a benign condition that can be surgically corrected. Nuclear imaging scintigraphy accurately localizes the tumor in 90% of cases and simplifies the surgical management. We encountered two such cases with the parathyroid gland adenomas who presented to us in two different varied presentations, in which preoperative nuclear imaging and intraoperative parathyroid hormone (PTH) assay played a major role. The two different cases also drew us to the important aspect of Hungry bone syndrome (HBS) which was encountered in the postoperative period, in which the role of pediatric endocrinologist is of paramount importance.

CASE REPORTS

CASE 1

A 12-year-old girl presented with a 2-week history of worsening epigastric pain, vomiting, and fever. She was treated in outside hospital on the lines of gastroenteritis; however, as the vomiting did not subside, she was referred to our hospital for further management. On examination, she was pale with dry mucous membranes. At admission, she had bradycardia (heart rate 68/min) and hypotension (blood pressure 90/60 mm of Hg) with an increased respiratory rate (24/min). Musculoskeletal system examination revealed muscle weakness of both the lower limbs (power 4/5), with the presence of genu valgum. There were no evidence of any bony pain and no palpable lumps in the neck. Laboratory investigations showed features of hypercalcemia with hyperparathyroidism [Table 1]. An ultrasound scan of her neck revealed a 2.2 cm × 1.4 cm well-defined oval hypoechoic mass in the posteroinferior aspect of the left lobe of thyroid gland. Radionuclide parathyroid scintigraphy, performed with 600 MBq of Tc-99m sestamibi, highlighted the adenoma in the left inferior parathyroid which persisted after 2 h of washout period [Figure 1].

Table 1

Laboratory parameters of cases

Figure 1

Tc-99m sestamibi scan showing adenoma in the left inferior parathyroid gland

The patient underwent initial conservative management with aggressive intravenous fluid resuscitation, intravenous loop diuretic treatment, and intravenous bisphosphonate therapy. On day 5, biochemical markers had improved and serum calcium had stabilized. The patient underwent a neck exploration on day 6, and left upper parathyroidectomy was performed with intraoperative PTH assay. Histological examination of the excised gland confirmed it to be a benign adenoma.

The patient recovered well postoperatively, with PTH levels normalizing within a day. Subsequent recovery included a period of hypocalcemia, which resolved over a period with injection calcium gluconate, followed by oral calcium and activated Vitamin D (rocaltrol) replacement within a month. Three months after the surgery, her serum calcium is 9.5 mg/dl, the proximal muscle weakness has improved, and she is now to her normal daily routine.

CASE 2

A 13-year-old girl presented with a 2-week history of progressive painful limp following a dance recital along with intermittent pain in the left knee and hip. She was treated in outside hospital on the lines of arthritis; however, as the pain did not subside, she was referred to our hospital for further management. Examination of the musculoskeletal system revealed tenderness of left hip, diffuse tenderness over left thigh with muscle weakness of both the lower limbs (power 4/5), and presence of genu valgum. There was no evidence of palpable lump in the neck. Laboratory investigations showed evidence of hypercalcemia with hyperparathyroidism [Table 1].

X-ray of the pelvis and left hip joint showed evidence of Looser's zone [Figure 2]. An ultrasound scan of her neck revealed a 1.2 cm × 1.4 cm well-defined oval hypoechoic mass in the posteroinferior aspect of the left lobe of thyroid gland. Radionuclide parathyroid scintigraphy, performed with 600 MBq of Tc-99m sestamibi, highlighted the adenoma in the left inferior parathyroid which persisted after 2 h of washout period. The patient underwent a neck exploration and left upper parathyroidectomy was performed with intraoperative PTH assay. Histological examination of the excised gland confirmed it to be a benign adenoma.

Figure 2

X-ray of the pelvis showing evidence of Looser's zone

The patient recovered well postoperatively, with PTH levels normalizing within a day. Subsequent recovery included a period of hypocalcemia, which resolved over a period with injection calcium gluconate, followed by oral calcium and activated Vitamin D (rocaltrol) replacement within a month. Three months after the surgery, her serum calcium has normalized, the proximal muscle weakness has improved, and she is now to her normal daily routine.

DISCUSSION

Primary hyperparathyroidism is a rare disease, where the majority of patients now present asymptomatically with a mildly raised serum calcium and marginally elevated PTH level.[2] However, our case highlights two important aspects of parathyroid disease that the authors would like to highlight. First, the difficulty was faced preoperatively in the management of a patient presenting with hyperparathyroid crisis and managing the same patient postoperatively for hypocalcemia due to HBS.

Parathyroid crisis is a life-threatening emergency. It is also known in literature as acute hyperparathyroidism, parathyroid storm, parathyrotoxicosis, acute parathyroid intoxication, hypercalcemic crisis, and calcium intoxication. It was first described in 1923 by Dawson and Struthers.[3] It is characterized by severe hypercalcemia (>14 mg/dL or >3.5 mmol/L) associated with signs and symptoms of multiorgan failure.[3] Although most cases of severe hypercalcemia are seen in malignancy, it is important to emphasize that severe hypercalcemia with raised PTH is pathognomonic of primary hyperparathyroidism.[4] Patients with parathyroid crisis demonstrate gastrointestinal and neurological symptoms, renal failure, and cardiac rhythm abnormalities. Our patient had very high corrected serum calcium level of 17.7 mg/dL. She exhibited gastrointestinal features such as nausea, vomiting, and epigastric pain.

Management of hyperparathyroid crisis has traditionally involved an emergency parathyroidectomy within 72 h of presentation, which has a mortality of up to 14%.[5] However, recent evidence published by Phitayakorn and McHenry[5] supports an early excision after a period of stabilization with loop diuretics and intravenous bisphosphonate therapy, rather than emergency surgery. This relatively rapid reduction in serum calcium thereby acts as a “bridge to surgery,” with a mean interval between presentation and operative intervention of 8 days.[5] This is not dissimilar to our interval of 6 days, thereby allowing for appropriate operative workup and management of concurrent medical problems. Surgical management of patients presenting with hyperparathyroid crisis secondary to adenomatous disease is effective, with a reported success rate of 92%.[6] With appropriate medical management before surgical excision, mortality rates have fallen with rates for patients presenting in hyperparathyroid crisis reported as 2.8%.[7] In our patient, we medically optimized before surgically excising the tumor.

The parathyroid surgery has evolved over the years because of development of preoperative localization techniques which include high-resolution radiographic techniques and rapid intraoperative parathyroid hormone (IOPTH) assay. The development of IOPTH assay was an important advancement in surgical management of parathyroid adenoma.[8] The success of this approach is based on the fact that PTH has a half-life of 5 min. A drop in IOPTH levels of >50% from the baseline or presurgical excision value at 10 min after gland excision is accepted as the criterion by which the surgeon could conclude that all abnormal glands had been removed, without any need to identify all four glands.

HBS refers to the rapid and prolonged hypocalcemia associated with hypophosphatemia and hypomagnesemia, which is exacerbated by suppressed PTH levels, which follows parathyroidectomy in patients with severe primary hyperparathyroidism. The syndrome is reported in 25–90% of patients with radiological evidence of hyperparathyroid bone disease versus only 0–6% of patients without skeletal involvement. Treatment is aimed at replenishing the severe calcium deficit using high doses of calcium-supplemented by high doses of active metabolites of Vitamin D. Adequate correction of calcium deficiency and normalization of bone turnover are required for resolution of the hypocalcemia which may last for a number of months after successful surgery.[9]

In summary, our cases highlight to the different protean manifestations of parathyroid adenoma which may lead to misdiagnosis in early stages of disease as evident in both of our cases. Primary hyperparathyroidism, with its varied manifestations and indolent course, is a condition well-known to pose a diagnostic dilemma to the clinician, in which a high index of suspicion alone often leads to a proper diagnosis and timely management. Preoperative scintigraphy helped in confirming the location of the adenoma and intraoperative parathyroid assay simplified the surgical management in this case which otherwise would have been a challenging task for operating surgeon.

FINANCIAL SUPPORT AND SPONSORSHIP

Nil.

CONFLICTS OF INTEREST

There are no conflicts of interest.