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Two Causes of Hypercalcemia: Learning by the Holmesian Method

2004; Elsevier BV; Volume: 79; Issue: 5 Linguagem: Inglês

10.4065/79.5.708

1942-5546

B. Sopeña, Gustavo Rodríguez, Javier de la Fuente, C. Martínez-Vázquez,

Clinical Reasoning and Diagnostic Skills

To the Editor: Because medical reasoning has a detective-like quality,1Vandenbroucke JP In defense of case reports and case series.Ann Intern Med. 2001; 134: 330-334Crossref PubMed Scopus (386) Google Scholar the Sherlock Holmes method based on detailed history and careful examination2Doyle AC A study in scarlet.in: The Complete Sherlock Holmes. Doubleday, Garden City, NY1960: 23-24Google Scholar can help physicians solve problems and avoid errors. We agree with Holmes’ statement: “Deceit is an impossibility in the case of one trained to observation and analysis.”2Doyle AC A study in scarlet.in: The Complete Sherlock Holmes. Doubleday, Garden City, NY1960: 23-24Google Scholar This positive attitude in caring for patients requires attention and eliminates boredom, an important source of medical errors.3Leape LL Error in medicine.JAMA. 1994; 272: 1851-1857Crossref PubMed Google Scholar The Holmesian method teaches us to not “close” a case before all the data fit properly because clinicians have a tendency “to look for evidence that supports an early working hypothesis and to ignore data that contradict it.”3Leape LL Error in medicine.JAMA. 1994; 272: 1851-1857Crossref PubMed Google Scholar The following case report demonstrates the Holmesian approach to patient care. Report of a Case.—A 77-year-old woman was admitted to the hospital because of diffuse skeletal pain and pathologic bone fractures. The patient had hypertension that was well controlled with diet and valsartan. She had never taken thiazide diuretics or lithium. One month before admission, she experienced nonspecific diffuse chest pain that did not respond to nonsteroidal anti-inflammatory drugs; her general health deteriorated. On admission, the patient had muscle weakness and somnolence. Laboratory studies disclosed the following values: hemoglobin, 10.5 g/dL; mean corpuscular volume, 102 fL; erythrocyte sedimentation rate, 85 mm/h; creatinine, 0.9 mg/dL; calcium, 12.9 mg/dL; phosphorus, 3 mg/dL; and alkaline phosphatase, 323 U/L with normal transaminase levels. Serum ferritin, vitamin B12, folic acid, and lactate dehydrogenase levels were normal. Serum electrophoresis showed hypogammaglobulinemia (IgG, 344 mg/dL; IgA, 23 mg/dL; and IgM, 13 mg/dL). A bone scan revealed chondrocalcinosis of the knees and wrists and old fractures of the ribs and pelvis. Immunoradiometric assay showed an elevated intact parathyroid hormone value of 154.87 pg/mL (reference range, 10-65 pg/mL). Parathyroid hormone-related peptide, 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D3, and thyrotropin levels were normal. Ultrasonography of the neck showed a nodule adjacent to the inferior pole of the right thyroid lobe. During hospitalization, the patient experienced hypercalcemic crisis. Primary hyperparathyroidism (PHP) was diagnosed. Because an elevated erythrocyte sedimentation rate, anemia, and hypogammaglobulinemia are not typically seen in patients with PHP, we sought a complete explanation for these abnormalities. The patient had no signs or symptoms of temporal arteritis. Findings on abdominopelvic computed tomography and mammography were normal, and serum and urine immunofixation studies yielded negative results. A bone marrow aspirate contained 30% dismorphic plasmacytic infiltrates, and immunohistochemical study of a bone marrow biopsy specimen was positive for κ light chains in infiltrating plasma cells. Stage IA nonsecretory multiple myeloma (MM) was diagnosed. The patient refused surgery and chemotherapy. Although the hypercalcemia was well controlled with oral bisphosphonates, the MM progressed, and the patient died a year later. The coexistence of PHP with monoclonal gammopathy and MM has been described4Toussirot E Bille F Henry JF Acquaviva PC Coexisting kappa light chain multiple myeloma and primary hyperparathyroidism.Scand J Rheumatol. 1994; 23: 49-50Crossref PubMed Scopus (12) Google Scholar; however, a causal relationship has not been established.5Arnulf B Bengoufa D Sarfati E et al.Prevalence of monoclonal gammopathy in patients with primary hyperparathyroidism: a prospective study.Arch Intern Med. 2002; 162: 464-467Crossref PubMed Scopus (47) Google Scholar Usually, MM is diagnosed first, and PHP is suspected only when hypercalcemia persists despite treatment.4Toussirot E Bille F Henry JF Acquaviva PC Coexisting kappa light chain multiple myeloma and primary hyperparathyroidism.Scand J Rheumatol. 1994; 23: 49-50Crossref PubMed Scopus (12) Google Scholar Nonsecretory MM accounts for less than 3% of all cases of MM.6Kyle RA Gertz MA Witzig TE et al.Revew of 1027 patients with newly diagnosed multiple myeloma.Mayo Clin Proc. 2003; 78: 21-33Abstract Full Text Full Text PDF PubMed Scopus (1651) Google Scholar Without typical bone lesions, nonsecretory MM poses a clinical challenge, and an important diagnostic delay can occur. To our knowledge, this is the first reported case of concomitant PHP and nonsecretory MM. During our diagnostic work-up, we remembered Holmes’ advice: “Do you really think that your solution must be correct?…Does your explanation cover every point?”7Doyle AC The adventure of Black Peter.in: The Return of Sherlock Holmes. 159. Strand Magazine, London, England1904: 14-15Google Scholar Diagnostic hypotheses must be confirmed by clinical findings to “avoid missing the little points or fine details which are in the basis of the deduction.”8Kassirer JP Kopelman RI A defective detective.Hosp Pract (Off Ed). 1986; 21: 91-98PubMed Google Scholar In our case, PHP explained most, but not all, of the patient's abnormalities. Overt PHP masked underlying MM, the most serious condition in our patient, which eventually caused her death.