The patient at the center of the report was a 64-year-old woman with a history of diabetes mellitus, hypertension, and chronic kidney disease. She had no complaints whatsoever, no palpable thyroid nodule, no swollen lymph nodes, and no family history of thyroid cancer or other endocrine tumors. Her medullary thyroid carcinoma came to light only because an unrelated metabolic work-up revealed an isolated elevation of procalcitonin, a biomarker more commonly associated with severe bacterial infections. That incidental finding set in motion a diagnostic chain that ultimately uncovered a two-centimeter tumor in her left thyroid lobe, along with a second, entirely separate and unexpected cancer measuring just half a millimeter in the right lobe.

The diagnostic challenge in this case was considerable, and it illustrates why medullary thyroid carcinoma remains one of the most treacherous diagnoses in endocrinology. Roughly one quarter of cases arise in the setting of inherited syndromes such as multiple endocrine neoplasia type 2A and 2B or familial medullary thyroid carcinoma, all driven by germline mutations in the RET proto-oncogene. The majority of cases, however, are sporadic, and somatic RET mutations are found in about sixty percent of these tumors. The specific mutation involved matters enormously: the common p.Met918Thr alteration produces a markedly more aggressive course, while RET-negative tumors often carry RAS-family mutations instead. Because family history can be absent in up to half of hereditary cases, guidelines recommend germline RET screening even in patients who appear to have sporadic disease. In this particular patient, germline testing could not be performed, leaving an open question about whether an occult hereditary syndrome might have been at play.

Laboratory evaluation told an intriguing story. The woman’s serum calcitonin—the classic hallmark of C-cell derived tumors—measured 2100 nanograms per liter, and her carcinoembryonic antigen, or CEA, a glycoprotein used as a tumor marker, stood at 20.8 nanograms per milliliter. Yet neither of these values had triggered the initial investigation. Instead, it was procalcitonin that raised the alarm, and the report’s authors emphasize that this was no accident. Procalcitonin secretion is a recognized physiological product of thyroid parafollicular C cells, so once a C-cell neoplasm is present, its elevation is expected rather than surprising. In this patient, the procalcitonin signal happened to arrive first, in a clinical context—chronic kidney disease—where such an elevation could easily have been dismissed or misattributed.

The authors argue that the concurrent CEA elevation was actually the more diagnostically instructive finding. CEA is not specific to C cells, and an unexplained CEA rise in an older adult is conventionally pursued as a possible sign of gastrointestinal malignancy. Several previous reports have described medullary thyroid carcinoma presenting initially as an isolated CEA elevation that was ultimately traced back to the thyroid. In one directly comparable case, a patient with subclinical hyperthyroidism was found to have sporadic medullary thyroid carcinoma first suspected because of a high CEA level, with strong CEA immunoreactivity later confirmed on the surgical specimen. Larger retrospective series have also shown that preoperative CEA correlates with tumor size and stage, with concentrations above roughly 270 to 400 nanograms per milliliter associated with larger or metastatic disease. The modest CEA elevation in this new case fits neatly with the small, low-grade, node-negative tumor that pathology ultimately revealed.

Chronic kidney disease complicated the interpretation at every turn. Reduced renal clearance can independently cause mild elevations of both calcitonin and CEA, which means that in a patient like this, both markers could have been dismissed as artifacts of her kidney function. The report’s authors stress that calcitonin elevation in chronic kidney disease should never be reflexively attributed to impaired renal clearance alone, because excluding an underlying C-cell malignancy remains essential. Their message is a warning against a common diagnostic shortcut: in patients with kidney disease, an elevated calcitonin level demands the same rigorous work-up it would receive in anyone else, including neck imaging, fine-needle aspiration with calcitonin measurement in the washout fluid, and appropriate immunocytochemistry.

That work-up, in this case, was thorough. Neck ultrasonography showed solid hypoechoic nodules in both lobes. Fine-needle aspiration of the left lobe nodule was consistent with medullary thyroid carcinoma, with calcitonin detected in the needle washout and immunocytochemistry showing positivity for chromogranin A and CEA alongside negativity for thyroglobulin—the protein made by ordinary thyroid cells, whose absence helps distinguish medullary from other thyroid cancers. Computed tomography of the neck, thorax, and abdomen found no distant metastases, and a gallium-68 DOTATATE PET/CT scan, which images somatostatin receptor expression, showed uptake in the thyroid nodule and several cervical and axillary lymph nodes. The patient underwent total thyroidectomy with bilateral central neck dissection, and the surgery went without complication.

Pathology confirmed a two-centimeter, partially encapsulated, low-grade medullary thyroid carcinoma with negative surgical margins, no vascular or perineural invasion, and a Ki-67 proliferation index of just one percent. All seventeen dissected lymph nodes were free of metastasis. Tumor cells stained positive for calcitonin, CEA, chromogranin A, synaptophysin, and several other markers, with loss of CD56 expression. Interestingly, amyloid deposition—a classic pathological feature of medullary thyroid carcinoma—could not be demonstrated. And in a remarkable twist, an incidental 0.05-centimeter classic papillary microcarcinoma, an entirely different type of thyroid cancer, was found in the right lobe. After surgery, the patient’s biomarkers collapsed dramatically: calcitonin fell from 2100 to 3.1 nanograms per liter and CEA from 20.8 to 3.1 nanograms per milliliter, and at three-month follow-up she remained well.

Beyond this single patient, the report situates the case within a rapidly evolving field. Recent studies show that calcitonin’s immunohistochemical specificity is not absolute—calcitonin-positive staining in lung tissue has occasionally masqueraded as metastatic medullary thyroid carcinoma when the real lesion was a pulmonary neuroendocrine tumor. Research on imaging decisions suggests that a 500 picograms-per-milliliter calcitonin threshold for staging scans has high sensitivity but low specificity, and that models combining calcitonin with ultrasound findings of suspicious lymph nodes perform better than any single value. On the surgical side, data from nearly 400 patients indicate that lobectomy may be a safe option in selected sporadic cases without germline RET mutations, whereas total thyroidectomy remains essential in hereditary disease. For advanced cases, a network meta-analysis found that the selective RET inhibitor selpercatinib reduced the risk of progression by ninety percent compared with placebo, outperforming older multikinase inhibitors in both efficacy and tolerability, though acquired resistance through solvent-front mutations remains an emerging challenge.

The broader lesson from this case is that medullary thyroid carcinoma can remain entirely silent until an incidental biochemical abnormality—here an isolated procalcitonin elevation rather than the expected calcitonin trigger—prompts further evaluation. For clinicians managing patients with chronic kidney disease, the message is unambiguous: biomarker elevations deserve careful, layered interpretation rather than reflexive attribution to renal impairment. As the field moves toward individualized medicine built on genetics, organoid models, and refined imaging strategies, cases like this one serve as a reminder that the first step in precision oncology is often the oldest one—paying close attention to an abnormal number on a routine laboratory report, and refusing to stop until its meaning is fully understood.

Subject of Research: A case of asymptomatic medullary thyroid carcinoma presenting with isolated procalcitonin elevation in a patient with chronic kidney disease

Article Title: Asymptomatic Medullary Thyroid Carcinoma With Isolated Carcinoembryonic Antigen Elevation in a Patient With Chronic Kidney Disease: A Case Report

Article References: Altınyüzük, O., Ediz, B., Yalın, S. F., & Parmaksız, E. (2026). Asymptomatic Medullary Thyroid Carcinoma With Isolated Carcinoembryonic Antigen Elevation in a Patient With Chronic Kidney Disease: A Case Report. Clinical Case Reports, 14(9), Article e73580. https://doi.org/10.1002/ccr3.73580

Image Credits: AI Generated

DOI: 10.1002/ccr3.73580

Keywords: medullary thyroid carcinoma, procalcitonin, calcitonin, carcinoembryonic antigen, chronic kidney disease, RET proto-oncogene, thyroidectomy, biomarkers, neuroendocrine tumors, fine-needle aspiration, selpercatinib, case report