Authors : Mohammad Ebrahimi; Vera Ivanovna Nesterova

Volume/Issue : Volume 10 - 2025, Issue 1 - January

Google Scholar : https://tinyurl.com/mwppwwy5

Scribd : https://tinyurl.com/mpsruwp4

DOI : https://doi.org/10.5281/zenodo.14836680

Abstract : Hypothyroidism is a prevalent condition that can progress from subclinical to overt forms. Early detection of subclinical hypothyroidism is essential for effective and cost-efficient treatment, as well as for identifying risk factors that may prevent disease progression. While TSH is the standard first-line screening test, its levels can be misleading due to various factors, and thyroid ultrasonography, though useful, has limitations. This article explores the use of 3D-NLS bio-resonance feedback diagnostics for the early detection of subclinical hypothyroidism, focusing on biophysical markers such as Fleindler’s Index (FI), Entropy Index, and Noise/Information Index (NII). The study compares these markers with ultrasound criteria and biochemical parameters, including serum levels of T3, T4, TSH, and anti-TPO. Results indicate that the NLS-3D bio- feedback system effectively evaluates biophysical spectral-entropy parameters, revealing significant differences between the groups studied. The analysis demonstrates that Spectral Entropy Analysis (SEA) parameters are valuable for the early detection of thyroid-related disorders and can be utilized in screening asymptomatic patients.

Keywords : Sub-hypothyroidism, Screening, TSH, Ultrasound, 3D-NLS Bio Resonance Feed- Back Diagnostic, Spectral-Entropy- Analysis, Biophysical Markers.

References :

1. Chaker L, Bianco AC, Jonklaas J, Peeters RP (2027) Hypothyroidism. Lancet 390(10101):1550–1562
2. Unnikrishnan AG, Kalra S, Sahay RK, Bantwal G, John M, Tewari NI (2013) Prevalence of hypothyroidism in adults: an epidemiological study in eight cities of India. Indian J Endocrinol Metab 7(4):647–652
3. Krishan P and Singh Randhir (2011) Clinical perspective of hypothyroidism. Journal of Applied Pharmaceutical Science 01(5):64-68
4. Meier C, Trittibach P, Guglielmetti M, Staub J and Muller B (2003) Serum thyroid stimulating hormone in assessment of severity of tissue hypothyroidism in patients with overt primary thyroid failure: cross sectional survey. BMJ  326: 311-312
5. Calsolaro V, Niccolai F, Pasqualetti G, Calabrese AM, Polini A, Okoye C, et al (2019) Overt and Subclinical Hypothyroidism in the Elderly: When to Treat? Frontiers in Endocrinology 10(177):1-8
6. Imaizumi M, Akahoshi M, Ichimaru S, Nakashima E, Hida A, Soda M, et al (2004) Risk for ischemic heart disease and all-cause mortality in subclinical hypothyroidism. Journal of Clinical Endocrinology and Metabolism 89: 3365–3370
7. Kahaly GJ (2000) Cardiovascular and atherogenic aspects of subclinical hypothyroidism. Thyroid 10: 665–679
8. Knudsen N, Laurberg P, Rasmussen L B, Bulow I, Perrild H, Ovesen L & Jørgensen T (2005) Small differences in thyroid function may be important for body mass index and the occurrence of obesity in the population. Journal of Clinical Endocrinology and Metabolism 90: 4019–4024
9. Maraka S, Ospina NM, O'Keeffe DT, Espinosa De Ycaza AE, Gionfriddo MR, Erwin PJ, et al (2016) Subclinical hypothyroidism in pregnancy: a systematic review and meta-analysis. Thyroid 26: 580-590  
10. Casey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, Cunningham FG (2005) Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol 105(2) :239–245
11. Stagnaro-Green A, Abalovich M, Alexander E, et al (2011) Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid (21): 081-1125
12. Nazarpour S, Ramezani Tehrani F, Simbar M, Azizi F (2015) Thyroid dysfunction and pregnancy outcomes. Iran J Reprod Med 13 (7): 387-396
13. De Groot L, Abalovich M, Alexander E K (2012) Management of thyroid dysfunction during pregnancy and postpartum: An Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 97(8): 2543-2565
14. Eddy DM (1991) How to think about screening. In: Eddy DM, ed. Common screening tests, 1st ed. Philadelphia: American College of Physicians1–21
15. Herman CR, Gill HK, Eng J and Fajardo LL (2002) Screening for Preclinical Disease: Test and Disease Characteristics.  AJR 179:825–831 
16. Koulouri O, Moran C, Halsall D, Chatterjee K, Gurnell M (2013) Pitfalls in the measurement and interpretation of thyroid function tests. Best Practice & Research Clinical Endocrinology & Metabolism 27:745–762
17. Kwakkel J, Fliers E, Boelen A (2011) Illness-induced changes in thyroid hormone metabolism: focus on the tissue level. The Nederland Journal of Medicine 69 (5):224-227 
18. Zoccali C, Tripepi G, Cutrupi S, Pizzini P and Mallamaci F (2005) Low Triiodothyronine: A New Facet of Inflammation in End-Stage Renal Disease. JASN 16 (9): 2789-2795
19. Lee YK, Jo EK, Hyun JO, Kyung SP, Soo KK, Seok WP, Moon JK, and Yong WC (2011) Serum TSH Level in Healthy Koreans and the Association of TSH with Serum Lipid Concentration and Metabolic Syndrome. korean j intern med 26:432-439
20. Visser WE, Visser TJ, Peeters RP (2013) Thyroid Disorders in Older Adults. Endocrinol Metab Clin N Am 42 :287–303
21. Warade J, Pandey A (2014) Diurnal Variation of TSH: Factor Affecting Interpretation of Test. J Pharm Biomed Sci 04(09):776-780
22. John RK (2006) The Immune System as a Regulator of Thyroid Hormone Activity. Experimental Biology and Medicine 231(3): 229–236  
23. Mazer NA (2004) Interaction of estrogen therapy and thyroid hormone replacement in postmenopausal women. Thyroid 14(1): S27-34
24. Benencia H, Ropelato MG, Rosales M, Mesch V Siseles, N Boero, L Fogel, et al (1998) Thyroid profile modifications during oral hormone replacement therapy in postmenopausal women. Gynecol Endocrinol 12(3):179-84
25. Aghajanova LL, Lindeberg M, Carlsson IB, Stavreus-Evers A, Zhang P, Scott JE, et al (2009) Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue. Reprod Biomed 18:337–47  
26. Singh PA, Bobby Z, Selvaraj N, Vinayagamoorthi R (2006) An evaluation of thyroid hormone status and oxidative stress inundialyzed chronic renal failure patients. Indian J Physiol Pharmacol 50 :279–84.
27. Lim VS (2001) Thyroid function in patients with chronic renal failure. Am J Kidney Dis 38(1): S80–4
28. Hegedus L, Andersen JR, Poulsen LR, Perrild H, Holm B, Gundtoft E,  Hansen JM (1985). Thyroid gland volume and serum concentrations of thyroid hormones in chronic renal failure. Nephron 40:171–4
29. Chiu A C, Sherman SI (1998) Effects of pharmacological fiber supplements on levothyroxine absorption. Thyroid8 (8):667-71
30. Lilja JJ, Laitinen K, Neuvonen PJ (2005) Effects of grapefruit juice on the absorption of levothyroxine. Br J Clin Pharmacol 60(3):337-41 
31. Cohen-Lehman J, Dahl P, Danzi S, Klein I (2010) Effects of amiodarone therapy on thyroid function. Nat Rev Endocrinol 6(1):34-41
32. Laura S Ward (2010) The difficult patient: drug interaction and the influence of concomitant diseases on the treatment of hypothyroidism. Arq Bras Endocrinol Metab 54(5):435-442
33. Chaudhary V, Bano S (2012) Imaging of the thyroid: Recent advances. Indian J Endocrinol Metab 16:371–6
34. Vejbjerg P, Knudsen N, Perrild H, Laurberg P, Pedersen IB, Rasmussen LB, et al (2006) The association between hypoechogenicity or irregular echo pattern at thyroid ultrasonography and thyroid function in the general population. Eur J Endocrinol 155(4):547-52
35. Rago T, Chiovato L, Grasso L, Pinchera A & Vitti P (2001) Thyroid ultrasonography as a tool for detecting thyroid autoimmune diseases and predicting thyroid dysfunction in apparently healthy subjects. Journal of Endocrinological Investigation 24: 763–769
36. Loy M, Cianchetti ME, Cardia F, Melis A, Boi F & Mariotti S (2004) Correlation of computerized grey-scale sonographic findings with thyroid function and thyroid autoimmune activity in patients with Hashimoto’s thyroiditis. Journal of Clinical Ultrasound 32:136–140 
37. Feldman MK, Katyal S, Blackwood MS (2009) US artifacts. RadioGraphics 5:1179–1189
38. Massimiliano A, Chiara C, Luca P (2013) Standardized Ultrasound Report for Thyroid Nodules: The Endocrinologist’s Viewpoint. Eur Thyroid J 2:7–48
39. Geanina P and Jacqueline J (2012) Thyroid Nodules. Med Clin North Am 96(2): 329–349
40. Adrian G (2013) Detection of intraperitoneal free gas by ultrasound. AJUM16 2:56-61 
41. Lennart DJ (2002) Nonthermal Effects of Therapeutic Ultrasound: The Frequency Resonance Hypothesis. Journal of Athletic Training 37(3):293–299
42. Sleator RD (2010) The human superorganism - of microbes and men 74(2):214-5
43. Ebrahimi M, Nesterova VI and Nesterov VI (2017) New Three-Dimensional NLS-bio-feedback Approaches in Site Specific Diagnosis of Cancer. Springer International Publishing AG 2017,Cancer Genetics and Psychotherapy chapter 23: 1071-1098
44. Poletaev A and Ebrahimi M (2018) Unsolved Mysteries: from Reductionism to Holistic Approaches in Medicine: Lessons from Immunculus. Adv Biomed Res Innov12:1-6 
45. Vladimir IN, Sergey MP, Valeriy MV (2013) 3D NLS-method in vascular pathology diagnosis. CorSalud 5(3):237-239
46. Nesterova VI, Yankina LA, Kojemyakin OR (2012) Application of three-dimensional NLS-diagnostics in oncology. New trends and prospects of development FCO  3 (4); 19-21
47. Feldt-Rasmussen U, Hyltoft Petersen P, Blaabjerg O, Hørder M (1980) Long-term variability in serum thyroglobulin and thyroid related hormones in healthy subjects, Acta Endocrinol (Copenh) 95:328–34
48. Beckett G, MacKenzie F (2007) Thyroid guidelines – are thyroidstimulating hormone assays fit for purpose? Ann Clin Biochem 44(3):203–8
49. Fazio S, Palmieri EA, Lombardi G, Biondi B (2004) Effects of thyroid hormone on the cardiovascular system, Recent Progr Horm Res 59:31–50
50. Jill Tate and Greg Ward (2004) Interferences in Immunoassay. Clin Biochem Rev 25(2):105-120
51. Frost SJ, Hine KR, Firth GB, Wheatley T (1998) Falsely lowered FT4 and raised TSH concentrations in a patient with hyperthyroidism and human anti-mouse monoclonal antibodies. Ann Clin Biochem 35:317-20
52. Adel AA Ismail (2014) Identifying and Reducing Potentially Wrong Immunoassay Results Even When Plausible and “Not-Unreasonable”. Advances in Clinical Chemistry; Chapter Seven 66: 241-294
53. Waise A, Price HC (2009) The upper limit of the reference range for thyroid-stimulating hormone should not be confused with a cut-off to define subclinical hypothyroidism, Ann Clin Biochem 46:93–8
54. Khati N, Adamson T, Johnson K S, Hill MC (2003) Ultrasound of the thyroid and parathyroid glands. Ultrasound Q 19:162–176
55. Desser TS, Kamaya A (2008) Ultrasound of thyroid nodules. Neuroimaging Clin N Am 18 (3):463–478
56. Child S Z. Hartman C L, Schery L A, Carstensen E L (1990) Lung damage from exposure to pulsed ultrasound. Ultrasound Med Biol 16: 817–825
57. Dalecki D, Child SZ, Raeman CH, Cox C, Penney DP, Carstensen EL (1997a) Age dependence of ultrasonically induced lung hemorrhage in mice. Ultrasound Med Biol 23:767–776
58. Dalecki D, Raeman C, Child S, Cox C, Francis C, Meltzer R, Carstensen E (1997b) Hemolysis in vivo from exposure to pulsed ultrasound. Ultrasound Med Biol 23:307–313
59. Zachary JF, O’Brien W D Jr (1995) Lung lesions induced by continuous- and pulsed-wave (diagnostic) ultrasound in mice, rabbits, and pigs. Vet Pathol 32:43–54
60. Dalecki D (2004) Mechanical bioeffects of ultrasound. Annu Rev Biomed Eng 6 :229–248
61. Miller DL, Averkiou MA, Brayman AA, Everbach EC, Holland CK, Wible JH, Wu J (2008) Bioeffects considerations for diagnostic ultrasound contrast agents. J Ultrasound Med27:611–632
62. Miller M, W Brayman A, A Sherman T, A Abramowicz J, S Cox C (2001) Comparative sensitivity of human fetal and adult erythrocytes to hemolysis by pulsed 1 MHz ultrasound. Ultrasound Med Biol 2001; 27:419–425
63. Eddy DM. Screening for cervical cancer (1990) Ann Intern Med 113(3):214-26
64. Eddy DM. Screening for breast cancer (1989) Ann Intern Med 111(5):389-99
65. Garber AM, Sox H C Jr, Littenberg B (1989) Screening asymptomatic adults for cardiac risk factors: the serum cholesterol level. Ann Intern Med 110 (8):622–639
66. Sox HC Jr, Littenberg B, Garber AM (1989). The role of exercise testing in screening for coronary artery disease. Ann Intern Med 110:456–469