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

The core financial argument is striking. According to the authors’ estimates, a representative 200-bed community hospital that implements all five interventions could generate approximately $2.5 million to $2.8 million in annual laboratory and clinical savings. Beyond those direct savings, hospitals that improve their baseline performance on quality metrics could reduce penalties under the Centers for Medicare and Medicaid Services Hospital-Acquired Condition program by an estimated $200,000 to $600,000. The interventions may also improve publicly reported healthcare-associated infection metrics and strengthen hospital reputation, benefits that carry real competitive weight in an era when patients and payers increasingly scrutinize quality data.

Diagnostic stewardship, at its heart, is about ensuring the right test is ordered for the right patient at the right time—and that results are interpreted appropriately once they return. It is a discipline aimed at eliminating the cascade of harm that follows unnecessary or poorly targeted testing: false-positive results that trigger unneeded antibiotics, incidental findings that lead to invasive follow-up procedures, prolonged hospital stays, and wasted laboratory resources. Unlike efforts to restrict care, diagnostic stewardship refines decision-making at the moment a test is considered, making it an attractive target for both clinicians and administrators seeking measurable improvement.

The guide examines five common opportunities for improvement that recur across hospital settings. The first is optimizing testing for Clostridioides difficile, the bacterium responsible for severe, sometimes life-threatening diarrheal infections in healthcare settings. Because molecular assays can detect the organism in patients who are merely colonized rather than truly infected, testing unformed stools indiscriminately inflates infection rates and drives unnecessary treatment and isolation. The second and third targets are optimizing urine culture use and de-implementing unnecessary procalcitonin testing. Urine cultures ordered in patients without symptoms frequently reveal asymptomatic bacteriuria, a common finding that is often inappropriately treated with antibiotics, fueling resistance and adverse drug events. Procalcitonin, a biomarker sometimes used to guide antibiotic decisions, is frequently ordered in situations where the result will not change management, consuming resources without benefiting patients.

The remaining two interventions address the explosive growth of multiplex diagnostics. Optimizing respiratory pathogen panel use tackles panels that test for dozens of viruses and bacteria simultaneously in patients whose care would change little based on the full results, encouraging clinicians instead to select narrower panels or targeted tests matched to the clinical question. Optimizing blood culture use rounds out the list, addressing the widespread practice of drawing blood cultures from patients with low pretest probability of bloodstream infection or from indwelling lines where contamination is likely. Each unnecessary culture carries costs in laboratory processing, false-positive contamination that prompts additional testing and antibiotics, and extended lengths of stay when ambiguous results are reflexively treated.

For each of the five interventions, the authors lay out implementation strategies, projected financial impact, and practical examples that hospitals can adapt to their own circumstances. The financial models are designed to translate clinical improvements into the language of hospital administration: avoided laboratory costs, reduced antibiotic expenditures, shortened lengths of stay, and improved quality measure performance. That translation matters, because diagnostic stewardship programs typically require upfront investment in education, electronic health record modifications, and personnel time, and program champions must often justify those costs to budget-conscious executives before any savings are realized.

Senior author Sarah E. Turbett, MD, framed the resource as a bridge between clinical value and operational performance. Healthcare leaders know that every investment must improve both patient care and operational performance, she noted, and this framework helps hospitals evaluate and implement diagnostic stewardship in ways that improve clinical outcomes, strengthen quality metrics, and demonstrate measurable value. The emphasis on measurable value reflects a growing recognition that programs perceived as purely clinical initiatives often struggle to survive budget cycles, while those with robust business cases secure sustained institutional support.

The publication arrives at a moment when diagnostic excellence is receiving increasing national attention. The Centers for Disease Control and Prevention’s Core Elements of Hospital Diagnostic Excellence identifies diagnostic stewardship as a key strategy for improving diagnosis while advancing healthcare quality, safety, and value-based care. By aligning its guidance with that national framework, SHEA positions diagnostic stewardship as a central pillar of hospital quality improvement rather than a niche laboratory concern, giving infection preventionists, laboratory directors, and antimicrobial stewardship teams a shared vocabulary for engaging executive leadership.

The guide was developed by SHEA’s Diagnostic Stewardship Special Interest Group, a body convened specifically to advance this field, and it is aimed at a broad professional audience: healthcare executives, laboratory leaders, infection prevention professionals, antimicrobial stewardship teams, and frontline clinicians. Each of these groups plays a distinct role in making diagnostic stewardship succeed. Executives control the resources, laboratory leaders understand the technical nuances of test performance and utilization, infection prevention teams track the downstream effects on healthcare-associated infection metrics, stewardship programs connect testing behavior to antibiotic use, and clinicians ultimately decide which tests to order and how to interpret them.

For hospitals weighing whether to act, the combined figures offer a compelling bottom line. Direct savings of $2.5 million to $2.8 million annually, plus up to $600,000 in avoided CMS penalties, represent the kind of return that few quality initiatives can match—achieved largely by doing fewer, better-targeted tests rather than buying new technology. The authors emphasize that actual results will vary with each hospital’s baseline performance, patient population, and existing stewardship infrastructure, which is precisely why the guide insists on institution-specific business cases rather than one-size-fits-all projections. What the resource makes clear is that diagnostic stewardship has matured from a conceptual ideal into an operational discipline with documented strategies, modeled financial impact, and demonstrated potential to improve patient care, healthcare quality, and hospital finances simultaneously. As pressure mounts to deliver safer, higher-value care, the guide suggests that one of the most powerful tools available to hospitals may be simply ordering the right test, for the right patient, at the right time.

Subject of Research: Building hospital business cases for diagnostic stewardship interventions to improve patient care and reduce costs

Article Title: SHEA publishes resource to help hospitals build the business case for diagnostic stewardship

Article References: SHEA publishes resource to help hospitals build the business case for diagnostic stewardship. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: diagnostic stewardship, SHEA, hospital savings, Clostridioides difficile testing, urine culture, procalcitonin, respiratory pathogen panels, blood culture, antimicrobial stewardship, CMS penalties, healthcare quality, infection prevention