Persistently elevated procalcitonin leading to the diagnosis of medullary thyroid carcinoma: a surgical case report Open Access

Abstract

Introduction

Medullary thyroid carcinoma (MTC) accounts for 3%–5% of thyroid carcinomas and originates from parafollicular C cells that produce calcitonin [1, 2]. Diagnosis is typically confirmed by increased calcitonin levels [1, 3]; however, procalcitonin (PCT)—the prohormone of calcitonin, normally produced in small quantities by neuroendocrine cells—may serve as an alternative or complementary marker [4–7].

This case explores the diagnostic role of PCT as an early indicator of MTC in a patient presenting with recurrent biliary colic and persistently elevated PCT levels in the absence of infection.

Case presentation

The patient was a 63-year-old man residing in Calabria, with no family history of thyroid disease, a former smoker for over 10 years, and undergoing treatment for hypertension. His medical history included gallstone disease, with three recent emergency room visits for recurrent biliary colic.

During these episodes, PCT levels were markedly elevated (up to 16.8 ng/ml). The patient was initially hospitalized in the short-stay observation unit with a presumptive diagnosis of cholecystitis, despite the absence of clinical or radiological signs of infection. He was discharged after 24 h with empirical antibiotic therapy.

Two months later, he presented again with similar symptoms and persistently elevated PCT levels (>6.7 ng/ml). After stabilization and symptom resolution, he was discharged without a definitive diagnosis. Approximately 15 days later, he returned for a third episode of biliary colic.

A surgical consultation was requested. Clinical examination of the chest and abdomen was unremarkable, with no signs of infection. However, due to persistently high PCT values, the patient was admitted to the surgical ward for further evaluation.

Upon admission, the working diagnosis was gallbladder empyema, although no imaging or laboratory evidence supported this. Ceftriaxone therapy was initiated, and an infectious disease consultation was obtained. A chest computed tomography scan revealed a multinodular goiter with a dominant 2 cm nodule in the left thyroid lobe. Given the abnormal PCT levels, thyroid pathology—particularly MTC—was suspected.

Laboratory tests showed:

• Thyroid-stimulating hormone (TSH): 1.8 μU/ml (within normal range)

• Calcitonin: 250 pg/ml (markedly elevated)

• Thyroglobulin: within normal range

• PCT: 4.5 ng/ml

• Fine-needle aspiration cytology: TIR 3B (suspicious for malignancy)

The patient underwent endocrinological evaluation and otolaryngological assessment, including rigid fiberoptic laryngoscopy (RFLS) to verify vocal cord mobility.

Based on these findings, a total thyroidectomy with central compartment lymphadenectomy was performed using the intraoperative neuro-monitoring (NIM) system for intraoperative monitoring of the recurrent laryngeal nerves.

Preoperative laboratory results:

• FT4: 0.91 ng/dl (reference range 0.80–1.90)

• TSH: 0.06 μU/ml (reference range 0.40–4.00)

• Leukocytes: 10.87 × 10³/μl

• TSH receptors: <0.80

• PCT: 16.8 ng/ml

These findings indicated a suppressed TSH with normal FT4, consistent with subclinical hyperthyroidism, and markedly elevated PCT—suggesting a neuroendocrine origin rather than infection.

Final histological examination

Histopathological analysis confirmed MTC, characterized by an intraparenchymal subcapsular neoplasm with disease-free margins. Immunohistochemistry showed:

• Calcitonin: strongly positive

• Thyroglobulin: mildly positive

• CD56: positive

• Synaptophysin: positive

• No lymph node metastases were identified (0/9).

Follow-up

Follow-up, conducted in collaboration with endocrinologists, ENT specialists, and oncologists, showed normalization of calcitonin and PCT levels by postoperative day 2. Carcinoembryonic antigen (CEA) remained within normal limits, and genetic screening for multiple endocrine neoplasia (MEN) syndromes was negative. Postoperative RFLS confirmed normal vocal cord motility, consistent with the intraoperative NIM results.

Discussion

This case demonstrates how a persistently elevated PCT level in the absence of infection can serve as an early and unexpected indicator of MTC [4–6, 8]. While calcitonin remains the primary biochemical marker for MTC, our report highlights a scenario in which PCT was the only repeatedly abnormal parameter prompting further investigation.

The novelty of this case, compared with previously published evidence by Giovanella et al. and Vardarli et al., lies in the non-endocrine clinical context in which the abnormality emerged. Unlike the cohorts described by Giovanella, where PCT elevations were investigated within a targeted endocrine workup typically [4, 5, 9] in patients with known thyroid nodules or suspected thyroid disease—our patient presented repeatedly to the emergency department for biliary colic, with no clinical suspicion of thyroid pathology. The elevated PCT level was discovered incidentally, outside a thyroid-focused evaluation, and became the key trigger that ultimately directed clinicians toward the diagnosis of MTC. This atypical diagnostic pathway underscores the importance of considering endocrine causes when PCT remains unexplained.

The pathophysiological basis for elevated PCT in MTC is linked to its origin as the prohormone of calcitonin. Under normal conditions, PCT is processed into calcitonin within parafollicular C cells [4, 8, 10]. Neoplastic transformation disrupts this maturation pathway, leading to aberrant synthesis and direct secretion of PCT into the bloodstream [2, 11]. This mechanism explains the occurrence of elevated PCT levels in MTC independently of infectious stimuli, as well as the rapid normalization of PCT following tumor removal, as observed in our patient.

When confronted with occult PCT elevation, clinicians must consider a broad differential diagnosis beyond infection. Non-infectious causes include neuroendocrine tumors [10] (e.g. small-cell lung carcinoma, pancreatic neuro-endocrine tumors (NETs), severe systemic inflammation (trauma, burns, pancreatitis), renal impairment, autoimmune diseases, and drug-related effects. In this case, the absence of any systemic inflammatory signs, normal imaging, and lack of alternative explanations strengthened the suspicion of an underlying neuroendocrine malignancy.

Despite its potential usefulness, PCT has limitations as a biomarker for MTC. It lacks specificity, as elevations may occur in numerous non-infectious and non-malignant conditions [6]. Additionally, unlike calcitonin, PCT does not have standardized, validated cut-off values for the diagnosis of MTC, and inter-assay variability may complicate interpretation [6]. Therefore, PCT should be considered a complementary, rather than primary, biomarker and must be interpreted in conjunction with calcitonin, CEA, clinical findings, and imaging studies.

Existing literature—including works by Giovanella et al. (2010, 2021, 2022), Vardarli et al. (2021), and the ATA guidelines (Wells et al., 2015)—supports an emerging role for PCT both in diagnosis and postoperative monitoring of MTC [1, 4–6, 8]. Our case adds to this evidence by illustrating an unusual diagnostic scenario in which PCT elevation preceded any thyroid-specific investigation and ultimately facilitated timely surgical management.

In summary, persistent PCT elevation without infectious or inflammatory signs should prompt consideration of medullary thyroid carcinoma among the differential diagnoses. A combined approach incorporating both calcitonin and PCT may enhance diagnostic accuracy and improve clinical decision-making [4, 6, 8]. Further multicenter studies are needed to standardize the use of PCT in endocrine oncology and to define its role in routine practice.

Conflict of interest statement

None declared.

Funding

None declared.

References