Delay in the prescription of IVD laboratory tests could be hazardous
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant.
AGD Biomedicals (Pvt) LTD. Andheri East, Mumbai.
In order to improve patient outcomes, laboratory tests should be appropriately ordered, conducted using total quality management (TQM), reported in a timely manner, interpreted correctly and appropriately used for diagnosis and treatment of a patient(1). On-time tests could minimise the risk of growing health problems, as well as prevent related complications. However, when practicing physicians remain over-dependent on clinical experience, and clinical judgement, rather than ordering IVD clinical laboratory tests; during very early stage of a disease could be risky(2,3). (Refer to Case study Parts 1 and 2). Experience, individual belief systems, level of continues medical education (CMEs), the cost of laboratory tests, patient reassurance of cost-effective treatment, fear of litigation, health policy related matters and organization-related factors generally lead to reluctance of physicians to use clinical laboratory tests regularly to diagnose a specific case(2).
CASE STUDY – PART 1
A 52-year-old-man, an entrepreneur and apparently healthy individual (72 kg weight, 5’7’’ height) presented with loss of appetite, fatigue, and occasional mild fever during night hours. General practitioner prescribed supplements to improve appetite and antipyretic drugs. Following six months, same treatment was suggested to improve appetite and control mild fever at night hours and no IVD clinical laboratory tests were prescribed. After six months, patient lost significant weight (7 kg), his throat looked enlarged and he could not turn his head comfortably. He decided to seek second opinion. The following laboratory tests and radiological investigation were prescribed: CBC, ESR, Thyroid function tests and Chest X-ray. The test values were as follows:
COMPLETE BLOOD COUNT (CBC)
| PARAMETER | VALUE | REFERENCE RANGE (NORMAL RANGE) |
| Hemoglobin | 13.2 g | 13-17 g |
| Total WBC count | 7,800 per µl | 5000-10,000 per µl |
| Differential WBC count | ||
| Neutrophils | 60% | 40-75% |
| Lymphocytes | 36% | 20-45% |
| Eosinophils | 02% | 1-4 % |
| Red blood cell indices | ||
| (MCV, MCH, MCHC) | Normal findings | |
| Erythrocyte Sedimentation Rate (ESR) | 110 after 1 hr (Westergren method) | 0-15 mm, after 1hr. |
THYROID FUNCTION TESTS
| PARAMETER | VALUE | REFERENCE RANGE (NORMAL RANGE) |
| Serum T3 | 190 ng/dl | 86-187 ng/dl |
| Serum T4 | 16.8 µg/dl | 4.7-12.5 µg/dl |
| TSH | 0.2 µIU/dl | 0.3-5.0 µIU/dl |
CHEST X-RAY FINDINGS
| Significant accumulation of Plural fluid |
EXAMINATION OF PLEURAL FLUID
| Presence of Gram positive bacteria |
ACID-FAST STAINING
| Acid-Fast bacilli were detected |
Q1. What is the probable diagnosis?
ANS:
(1) Very high values of ESR, plural fluid accumulation due to lung infection and detection of Acid-Fast bacilli indicate that patient was suffering from Pulmonary tuberculosis.
(2) Significantly increased T3 and T4 and decreased TSH indicate Hyperthyroidism.
Note: Increased levels of plasma proteins such as fibrinogen, C-reactive protein, globulins, and decrease in albumin in acute and chronic infections (responsible for tissue damage and state of inflammation) increase red blood cell sedimentation (due to rouleaux formation) leading to high ESR.
CASE STUDY – PART 2
Antituberculosis drugs were prescribed and the patient was referred to a surgeon for thyroid examination. Thyrotoxicosis was diagnosed and thyroidectomy was advised to prevent thyrotoxicosis later on leading to thyroid cancer(4). However, histopathology examination of thyroid tissue was not recommended. After thyroidectomy, during next three months, treatment of TB continued with appropriate supplements to protect the patients from the side-effects of thyroidectomy. About 1,900 ml of plural fluid was removed in following three months the patient lost further about 10 kg weight. During this phase he also complained of failing vision and by the end of third month after thyroidectomy, he lost vision. He was referred to a ophthalmologist. Treatment was given to improve patient’s eyesight. No specific diagnosis was made and specific IVD laboratory tests were not prescribed. One of his client was a Medical Biochemist, who suggested the following laboratory tests:
| PARAMETER | VALUE | REFERENCE RANGE (NORMAL RANGE) |
| Serum calcium | 5.8 mg/dl | 8.5-10.5 mg/dl |
| Serum inorganic phosphorus | 10.5 mg/dl | 2.5-5.0 µg/dl |
| Serum alkaline phosphatase | 72 IU | 20-80 IU |
NOTE: Normal serum alkaline phosphatase (ALP) and significantly increased serum inorganic phosphorus and low serum calcium indicate hypoparathyroidism. In bone diseases high values of ALP are observed with low values of serum inorganic phosphorus and serum calcium.
Q1. What is the biochemical basis for deranged calcium and inorganic homeostasis?
ANS: Deficiency of parathyroid hormones leads to deranged calcium and inorganic homeostasis. Four parathyroid glands are located on the back side of thyroid gland. Due to thyroidectomy, during the phase of reestablishment of parathyroid glands with related supplements also the calcium and phosphorus metabolism was severely affected leading to low serum calcium and very high inorganic phosphorus in blood circulation. High circulating inorganic phosphorus deposits in various organs and particularly the eye lens, causing diminished eye sight.
Note: It took nearly four years for the patient to gain al least 80% of vision back by continued subsequent treatment on regulation of calcium and phosphorus metabolism and due to normal course of calcium and inorganic phosphorus homeostasis.
Q2. What were the obvious reasons for the ordeal gone through by the patient?
ANS:
(1) IVD laboratory tests(5,6) and X-ray chest could have been prescribed during the first month of treatment. Timely diagnosis of TB could have prevented progression of the TB infection to thyroid gland, which rarely gets infected due to its high iodine content.
(2) Histopathology examination of thyroid tissue was not performed. Histopathology studies of thyroid tissue could have detected Mycobacterium tuberculosis infection and related diagnosis as ‘Infective thyroiditis’, which could have cured by appropriate antibacterial treatment and averted surgical removal of the thyroid gland, which lead to parathyroid gland destabilization.
(3) Serum calcium and inorganic phosphorus tests were not prescribed. Very high values of serum inorganic could have been pointed to the reason, why eyesight of the patient continued to diminish.
References
(1) Whiting P, Toerien M, de Sallis I, Sterne AC, Dieppe P, Egger M, Fahey T. A review identifies and classifies reasons for ordering diagnostic tests. J Clin Epidemiol 2007; 60: 918-919. [DOI] [PubMed].
(2) Sood R, Sood A, Ghosh AK. Non-evidence-based variables affecting physicians test-ordering tendencies: a systematic review. Neth J Med 2007; 65: 167-177. [PubMed].
(3) Smellie W. Demand management and test request rationalisation. Ann Clin Biochem 2012; 49: 323-336. [DOI] [PubMed].
(4) Alexandra L. Alvarez BA, Michelle Mulder MD, Rachel S. Handelsman BS, John I. Lew MD, FACS, Josefina C. Farra MD, FACS. High Rates of Underlying Thyroid Cancer in Patients Undergoing Thyroidectomy for Hyperthyroidism. Journal of Surgical Research, Volume 245, January 2020, Pages 523-528.
(5) Godkar PB, Godkar DP. Medical Biochemistry, Theory and Practicals (1st edition, 2024), CBS Publishers, New Delhi,India.
(6) Godkar PB, Godkar DP. Text book of Medical laboratory technology (4th edition, 2024), Bhlani Publishers, Mumbai. India.
