Authors: Ragnfríð Kannuberg Tórolvsdóttir, Elsubeth Marian Fossádal, Peter Schwarz, Herborg Líggjasardóttir Johannesen
Categories: Case Report, Case report, Faroe Islands, Giant parathyroid adenoma, Hypercalcemia, Parathyroidectomy
Source: Journal of Medical Case Reports
Authors: Ragnfríð Kannuberg Tórolvsdóttir, Elsubeth Marian Fossádal, Peter Schwarz, Herborg Líggjasardóttir Johannesen
Primary hyperparathyroidism is an endocrine disease and a common cause of nonmalignant hypercalcemia, often discovered incidentally in asymptomatic patients. The case reported herein illustrates that significant hormonal imbalances can present with unexpectedly mild clinical manifestations.
We describe a 47-year-old Caucasian male with two episodes of kidney stones and otherwise no symptoms of severe hypercalcemia. In our case, fasting emerged as a potential risk factor for the development of renal stones. The diagnosis was primary hyperparathyroidism. The intervention consisted of preoperative fluids and cinacalcet while awaiting surgery. Despite initial stability, the patient experienced a subsequent increase in ionized calcium and parathyroid hormone levels, becoming symptomatic with fatigue, tremors, and heart palpitations. This progression led to a diagnosis of a hypercalcemic crisis, and the plan was accelerated. An acute parathyroid scintigraphy and an ultrasound was performed and revealed a giant intrathoracic parathyroid adenoma. After surgical removal of the adenoma, he developed hungry bones and biochemical remission. The patient has received three extracorporeal shock wave lithotripsy treatments for a stone in the upper left kidney, but as of a computed tomography scan on 9 February 2024, the stone remains unchanged. Owing to the stone’s resistance to extracorporeal shock wave lithotripsy and the absence of symptoms, no further treatment is planned. Endoscopic laser treatment (retrograde intrarenal surgery) is an option, but for now, the situation will be monitored.
This case report underscores that extremely elevated levels of calcium and parathyroid hormone along with a rare giant parathyroid adenoma may not necessarily present with symptoms indicative of a calcium crisis. Additionally, management of such rare giant parathyroid adenomas requires careful monitoring and a tailored approach to address potential postsurgical complications such as hungry bone syndrome.
Primary hyperparathyroidism (PHPT) is a prevalent endocrine disorder and the most common cause of nonmalignant hypercalcemia. PHPT is characterized by excessive parathyroid hormone (PTH) secretion from the parathyroid glands, regardless of serum calcium levels [1, 7, 8]. The incidence is increasing, likely owing to improved detection methods [1]. PHPT is often discovered incidentally in the asymptomatic patient [4, 6]. Retrospectively, such patients often have had high normal or slightly elevated serum calcium levels for years before the PHPT diagnosis. Patients may experience diffuse symptoms affecting various organ systems, such as fatigue, memory difficulties, nausea, and muscle weakness. Occasionally, the disease is diagnosed with a kidney stone attack [9]. The most common cause of PHPT is a single adenoma [3]. Less than 1.5% of all adenomas are larger than 3.5 g [2]. The World Health Organization (WHO) classifies giant adenomas as those larger than 10 g [2]. A hypercalcemic crisis is a severe medical condition marked by dangerously high levels of calcium in the blood, which can lead to critical symptoms such as confusion, dehydration, and renal failure. The scenario illustrates that significant hormonal imbalances can present with unexpectedly mild clinical manifestations, contributing insights to the literature.
We describe a 47-year-old Caucasian male patient who presented to the emergency room in the Faroe Islands in 2017 with acute abdominal and flank pain.
The patient had followed a spiritual practice involving fasting for 10 days, consuming only water and vitamins. The abdominal and flank pain started when the patient resumed solid food. A kidney stone was suspected as the cause of the abdominal pain. The patient’s records did not specify consideration of alternative diagnoses for abdominal pain, and liver function tests were not performed. A computed tomography (CT) urography and follow-up biochemical tests were scheduled. The CT urography confirmed kidney stones. A biochemical evaluation revealed ionized calcium (iCa) of 1.60 mmol/L and parathyroid hormone (PTH) of 34.4 pmol/L. The results of the full biochemical tests are presented in Table 1. Later, the kidney stones passed spontaneously, but regrettably, it has come to our attention that no action was taken on the measurement of calcium and PTH levels.Table 1Biochemical and medical overviewOctober2022November2022November2022November2022November202222NovemberOP24 November0POD1POD2POD3POD4POD7POD35PODNovember2023iCalcium(1.18–1.32 mmol/L)1.951.832.272.292.212.392.371.951.741.451.281.13stabel1.27Total calcium(2.20–2.55 mmol/L)3.40PTH(1.6–6.9 pmol/L)132109163129141.56.710.28.625OHD(> 50 nmol/L)1760117DEXA scan(T-score) total BMD−0.76L2–L4/hip−1.76Creatinine(60–105 μmol/L)149174112Magnesium(0.70–0.95 mmol/L)0.720.590.62Phosphate(0.71–1.53 mmol/L)0.600.89Cinacalcet treatment(mg)303090CCCR (> 0.020)0.029NaCl (L)/24 hours4CalciumD + D21 g2 g2 g2 g0PTH parathyroid hormone, 25OHD 25-hydroxyvitamin D, CCCR calcium creatinine clearance ratio, CalciumD calcium and vitamin D tablets, D2 calcitriol tablets–1,25 dihydroxycholecalciferol, POD postoperative day
Five years later, in October 2022, the patient visited his general practitioner (GP), complaining of fluctuating abdominal pain lasting for 2 weeks. The patient’s main concerns were related to his episodes of kidney stones. Like in 2017, he had just ended a 10-day fasting period. The patient underwent blood tests, revealing elevated total serum calcium, PTH, and low 25-hydroxyvitamin D levels (Table 1). Vitamin D supplementation commenced at 35 mcg daily, and the patient was promptly referred to an endocrinologist. At the endocrinology clinic, the patient reported general well-being, aside from a past kidney stone incident in 2017. The primary diagnosis was primary hyperparathyroidism. No other family members had hypercalcemia or kidney stones. Further assessments, including a comprehensive biochemistry screening, a 24-hour urine calcium creatinine clearance ratio (CCCR), and a dual-energy x-ray absorptiometry (DEXA) scan, were conducted. The DEXA scan in November 2022 indicated a slightly lower than normal bone mineral density (Table 1).
The intervention consisted of preoperative intravenous fluids (IVF) and cinacalcet 30 mg once daily, and the patient continued with the previously recommended vitamin D supplementation while awaiting surgery. The patient was advised to consume 3–5 L of water daily. The patient had a weight of about 80 kg. Despite initial stability, a subsequent increase in ionized calcium levels occurred, accompanied by rising PTH levels. The patient became symptomatic, experiencing fatigue, tremors, and heart palpitations, ultimately leading to a diagnosis of a hypercalcemic crisis. Vital signs at this time were blood pressure 139/89, pulse 84 bpm, saturation 99% without O2 supplementation, and respiratory frequency 19 bpm. An electrocardiogram (ECG) showed sinus rhythm with heart rate of 86 bpm.
Hospitalization ensued with intensified treatment involving isotonic NaCl infusions and an escalated Cinacalcet dosage (30 mg three times daily). Despite these measures, hypercalcemic symptoms persisted. Owing to limitations in diagnostic and treatment capabilities in the Faroe Islands, the patient was transferred to the Department of Endocrinology at Rigshospitalet, Denmark.
In Denmark, acute parathyroid scintigraphy (Tc-99m-Sestamibi) and ultrasound on 22 November 2022 revealed a large intrathoracic adenoma (Fig. 1). Despite continued intensified treatment with Cinacalcet 30 mg three times daily and NaCl infusions, serum ionized calcium levels rose further. Emergency surgery on 24 November 2022 successfully removed a giant adenoma, measuring 60 × 35 × 24 mm^3^ and weighing 24 g, addressing the underlying cause of the hypercalcemia. The intervention was performed without any adverse or unanticipated events. Histopathological examination indicated a benign adenoma without signs of malignancy or inflammation.Fig. 1Parathyroid scintigraphy (Tc-99m-Sestamibi) showing a parathyroid adenoma detected posterior and caudal to the left thyroid lobe. Computed tomography describes the process of reaching mediastinum superius and dislocating the trachea. Measures 4.2 × 2.8 × 6 cm^3^
Adherence to postoperative care was meticulously monitored through regular follow-up appointments, which included serum calcium and parathyroid hormone (PTH) level assessments. The patient was well informed about the importance of following medical advice, including prescribed medications and dietary guidelines, to support recovery and maintain normal calcium levels. Over the next 12 months, the patient received treatment involving 2 g of calcium and vitamin D supplementation. The patient’s positive engagement and adherence significantly contributed to the favorable outcome of the treatment. After 2 months, calcium homeostasis normalized, and after 3 months, the patient became asymptomatic with ionized calcium and PTH levels within normal reference values (serum ionized calcium level 1.24 mmol/L and PTH 7.1 pmol/L, respectively).
As of April 2024, 17 months postoperatively, the patient remains normocalcemic; calcium supplementation stopped after 12 months, and the patient is in good overall health. However, occasional flank pain persisted, and the patient has undergone extracorporeal shock wave lithotripsy (ESWL) treatment three times for stones in the upper left kidney pole. A CT scan performed on 9 February 2024, showed that the stone remains unchanged and had not passed. Discussions with the patient have clarified that some stones are too hard to be affected by ESWL. We typically do not pursue further treatment beyond three attempts per stone. There is an option for endoscopic transluminal treatment with laser (retrograde intrarenal surgery (RIRS)), but the patient reports no symptoms or discomfort from these stones in daily life. Consequently, we have decided to monitor the situation. He was advised to measure calcium values every year for the next 5 years at his GP. The patient expressed satisfaction with the treatment received. Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
The timeline information from this episode of care is organized in Table 1.
This case report highlights the presentation, diagnosis, and management of a Caucasian male with primary hyperparathyroidism (PHPT) and a rare giant parathyroid adenoma. Giant adenomas often present unique diagnostic and therapeutic challenges. Documenting these challenges, as well as successful approaches to overcoming them, can aid in expanding the knowledge base for healthcare professionals, fostering a deeper understanding of the complexities associated with these cases.
This case underscores the commonly observed diagnostic delay in patients with primary hyperparathyroidism (PHPT) presenting with nephrolithiasis [9]. Initially manifesting in 2017 with symptoms of kidney stone and elevated levels of iCa and PTH, unfortunately, subsequent biochemical tests did not include serum calcium and PTH, critical for averting diagnostic delay. Five years transpired from the initial presentation to the correct diagnosis.
In our case, fasting emerged as a potential risk factor for the development of renal stones, and fasting may be a risk factor for the development of renal stones [10]; however, other studies are warranted to investigate the relationship between fasting periods and the development or exacerbation of PHPT.
The patient in this case exhibited a notably low plasma vitamin D level, accompanied by the discovery of a massive 24 g adenoma and severe hypercalcemia upon PHPT diagnosis. Existing literature suggests an association between low vitamin D levels and the severity of PHPT, with some studies indicating that larger adenomas may be associated with reduced vitamin D levels [2]. However, it is essential to note that conflicting findings exist in literature, with some studies reporting no significant correlation between adenoma size and vitamin D levels [5].
Initially, the patient exhibited mild symptoms; however, treatment for hypercalcemia led to a severe hypercalcemic crisis, which required an emergency parathyroidectomy. This progression underscores that symptoms can escalate quickly, even when they are mild at first. Despite significant hormonal imbalances, clinical presentations can vary widely, emphasizing the importance of thorough diagnostic and management strategies. By sharing information about the clinical course, treatment outcomes, and followup of patients with giant adenomas, case reports contribute to the continuous improvement of patient care. The lessons learned from individual cases can inform best practices and potentially improve outcomes for patients with similar conditions in the future.
This case report demonstrates that extremely high levels of parathyroid hormone and a rare giant parathyroid adenoma do not always produce signs and symptoms characteristic of a calcium crisis. It emphasizes the need for personalized treatment plans, as the patient’s distinct clinical presentation and response to interventions suggest that standard treatment protocols may require modification based on individual patient factors.