Chapter 5. The Thyroid Nodule Epidemic

Chapter 5. 

A 36 Year Old Female With Hypothyroidism After Thyroidectomy

For Thyroid Cancer

Lisa, a 36 year old model and actress, arrived in my office and told me her story. Ever since her thyroidectomy for cancer, she has had symptoms of severe fatigue, muscle pain, hair loss, and dry skin. The small dose of Synthroid prescribed by her endocrinologist doesn't seem to be helping.  Four years ago, Lisa’s family doctor palpated her thyroid gland, thought he felt a nodule and sent her for thyroid ultrasound, “just to be sure".  The thyroid ultrasound images showed a small nodule about 9 mm in size, and the doctors recommended ultrasound guided needle biopsy, "just to be sure".  About a week after the biopsy, the pathology report came back with a diagnosis of "papillary carcinoma of the thyroid". 

Lisa is Told She Has Thyroid Cancer - Undergoes Thyroidectomy

As you can imagine, Lisa became upset and distraught when she learned from the doctor that she had thyroid cancer.  "Not to worry", said her doctor, “You have an excellent prognosis and a high likelihood for cure after surgery followed by radioactive Iodine treatment."  Grateful that she had a treatable cancer with a good prognosis, Lisa underwent the surgery and radiation.  Since the surgery completely removed her thyroid gland, she later required thyroid medication every day.  She also needed periodic screening tests to check for cancer recurrence.  Unfortunately, Lisa was not spared the adverse effects of her treatment. The surgery had disturbed her recurrent laryngeal nerve leaving her with a chronic hoarseness, cough and voice change.  The surgery also removed the parathyroid glands leaving her at risk for osteoporosis.  The radioactive iodine treatment caused salivary gland damage, leaving her with a chronic dry mouth and bad taste.  The radioactive Iodine also carried an increased generalized cancer risk over her lifetime, and of course, detrimental effect on fertility in the future when Lisa decides to have a family.

Switching from Synthroid to Natural Thyroid

I explained to Lisa that her symptoms of hypothyroidism were due to the miniscule dose of Synthroid, which was not enough to relieve her low thyroid symptoms.  In addition, Synthroid, which contains only T4, does not completely replace the function of her missing thyroid gland.  A natural thyroid medication made from desiccated porcine thyroid gland containing T3, T4 and Calcitonin is a far better alternative.  Lisa was switched over to her natural thyroid medication, called NatureThroid from RLC labs, along with Iodine supplementation, and 3 weeks later called the office to report a dramatic improvement with relief of chronic fatigue and improved energy levels.

A Cancer with No Biological Significance

For twenty years as an interventional radiologist, my job was to perform ultrasound needle biopsies of small thyroid nodules sent into the hospital by primary care doctors. The vast majority of thyroid cancers found with ultrasound scanning and needle biopsy are the small papillary carcinoma, a relatively benign tumor with excellent prognosis (30 year survival rate 95% ). (1)

A Frustrated Radiologist Says : Turn Off the Ultrasound Machines

An exasperated radiologist, John J. Cronan, MD says in the June 2008 issue of Radiology, “we should turn off the ultrasound machines".   Dr. Cronan questions this entire medical enterprise of detecting thyroid nodules, and small cancers with ultrasound guided biopsy.  "From the patient perspective, we have hung the psychological stigma of cancer on these patients and the dependency for daily thyroid supplementation...We accept all these consequences to control a cancer with a 99% 10-year survival."  (1-7)

A Normal Finding in Finland

Dr Harach says occult papillary carcinoma of the thyroid is a "normal" finding in Finland, and does not cause biologically significant disease. (8)  Dr. Louise Davies agrees with Dr Harach, and says in JAMA, "papillary cancers smaller than 1 cm could be classified as a normal finding" .(4)

Our Quixotic Approach to Thyroid Nodules

Keith Heller, MD, a neck surgeon who operated on 1,000 cases of thyroid cancer over a 28 year career, addressed his colleagues in a medical meeting saying: "I do not believe that this epidemic of (thyroid cancer) is real. It is due to ...the increasing use of ultrasound-guided needle biopsy of thyroid nodules. We may be diagnosing and treating cancers that have no clinical significance...We have embarked on a quixotic quest to rid our patients of microscopic and probably clinically unimportant thyroid cancer.... We are performing far too many unnecessary thyroidectomies. "(3)

Japan to the Rescue - Watchful Waiting

A thyroid cancer expert, Dr. Yasuhiro Ito of Kobe, Japan, has come up with a “watchful waiting” approach for papillary thyroid cancer.  Dr Ito published this statement in the 2003 Thyroid Journal: "Our preliminary data suggest that papillary microcarcinomas do not frequently become clinically apparent, and that patients can choose observation while their tumors are not progressing, although they are pathologically multifocal and involve lymph nodes in high incidence."   Dr Ito observed 162 patients with papillary thyroid microcarcinoma (< 10 mm) over 8 years.  70% of tumors either remained stable or decreased in size. Only 10% enlarged by more than 10 mm.  Only 1.2% of patients developed neck node metastasis over the 8 years observation. (26)  Because of this study, Dr. Ito says the patient can opt for watchful waiting with serial ultrasound follow up studies.  Dr Ito says that if follow up ultrasound shows enlarging tumor, or enlarging metastatic neck nodes, then more aggressive surgical treatment is indicated with an excellent prognosis.  In another study of 52 cases, Dr Ito found when the papillary thyroid cancer is resected as a benign nodule (by mistake), even this is sufficient treatment and no further immediate surgery is needed. (28)

It's the Pathologist's Fault - Just Stop Calling It Cancer

Perhaps this whole problem is caused by incorrect terminology used by the pathologist who reviews the biopsy slide and uses the word "cancer", a word that strikes fear and creates undue stress.  Once a pathology report with the word "cancer" is placed on the desk, rationality gets thrown out the window, and the patient demands aggressive treatment, usually out of proportion to the actual pathology.

In the 2003 issue of the International  Journal of Surgical  Pathology, Dr Rosai presented the Porto Proposal , in which he proposed a change in terminology. (23)(24)   Instead of the word, “cancer”, he suggested the terminology, papillary microtumor.   Others (Hazard et al.) proposed "nonencapsulated thyroid tumor" because "the surgeon may become unduly alarmed when the pathologist reports the presence of carcinoma." (46)  Harach et al. proposed the term occult papillary tumor, "in order to avoid unnecessary operations and serious psychologic effects on patients." (45)

Is Treatment of Papillary Micro-Carcinoma Overly Aggressive?

Over the years, we have seen surgical treatment for breast cancer evolve from the overly aggressive and debilitating radical mastectomy procedure, to the current day simple lumpectomy for many small breast cancers.  Perhaps treatment for thyroid cancer is going in this same direction, and is playing "catch-up" with the more limited breast cancer treatments.

Dr Ian Hay's 2008 study published in Endocrine Abstracts followed 900 patients with papillary thyroid microcarcinoma over 54 years. Dr Ian Hay, "neither total thyroidectomy, nor Postoperative Radioactive Iodine Ablation, improved long term outcome during 40 years, in terms of either tumor recurrence or cause-specific mortality." (17)  Dr Hay advocates removal of the tumor with unilateral lobectomy, saying that it was unnecessary to perform total thyroidectomy or radioactive iodine treatment, since they did not improve prognosis compared to unilateral thyroid lobectomy alone. (17)  In the future, I predict initial treatment for small papillary cancer of the thyroid gland will evolve into a simpler procedure, namely, unilateral thyroid lobectomy, or removal or the nodule alone, without the additional treatment with radioactive iodine.

 The Role of Iodine Supplementation

You might ask the obvious question, "Thyroid nodules are found in 67% of the population.  What is causing this?"  I would suggest that the most likely explanation is subclinical iodine deficiency in the population.  Iodine deficiency causes thyroid enlargement (goiter), thyroid nodules, and thyroid cancer.  Thyroid cancer appears linked to Iodine deficiency in both animal models and humans. (12)  Studies have shown that iodine deficiency is associated with increased anaplastic thyroid cancer, the aggressive type unresponsive to treatment and associated with high mortality rate. (15)   Population studies in which iodine supplementation was given showed reduction in mortality from thyroid cancer. (11)  

For references and links, see my web site: www.bioidenticalhormones101.com

References for Chapter 5. The Thyroid Nodule Epidemic

(1) http://radiology.rsnajnls.org/cgi/content/full/247/3/602  Editorials - Thyroid Nodules: Is It Time to Turn Off the US Machines? by John J. Cronan, MD June 2008 Radiology, 247, 602-604.

(2) http://jcem.endojournals.org/cgi/content/full/87/5/1938  The Journal of Clinical Endocrinology & Metabolism Vol. 87, No. 5 1938-1940.  Nonpalpable Thyroid Nodules—Managing an Epidemic by Douglas S. Ross 

(3) http://archotol.ama-assn.org/cgi/content/full/133/7/639   Do All Cancers Need to Be Treated? The Role of Thyroglobulin in the Management of Thyroid Cancer - The 2006 Hayes Martin Lecture - Keith S. Heller, MD .  Arch Otolaryngol Head Neck Surg. 2007;133(7):639-643.

(4) http://jama.ama-assn.org/cgi/content/full/295/18/2164  Increasing Incidence of Thyroid Cancer in the United States, 1973-2002 by Louise Davies, MD, MS; H. Gilbert Welch, MD, MPH .  JAMA. 2006;295:2164-2167.

(5) http://www.aafp.org/afp/20030201/559.html  Thyroid Nodules by MARY JO WELKER, M.D., and DIANE ORLOV, M.S., C.N.P.  AAFP Magazine

(6) http://www.cmaj.ca/cgi/content/full/177/11/1383  CMAJ • November 20, 2007; 177 (11) Explaining the increasing incidence of differentiated thyroid cancer by Jacques How, MB ChB and Roger Tabah, MD  Jacques How is with the Division of Endocrinology and Roger Tabah is with the Department of Surgery, Montreal General Hospital, McGill University Health Centre, Montréal, Que.

(7) http://jama.ama-assn.org/cgi/content/full/295/18/2179   Managing Small Thyroid Cancers by Ernest L. Mazzaferri, MD. JAMA. 2006;295:2179-2182.

(8) http://www.ncbi.nlm.nih.gov/pubmed/2408737  Cancer. 1985 Aug 1;56(3):531-8. Occult papillary carcinoma of the thyroid. A "normal" finding in Finland. A systematic autopsy study. by Harach HR, Franssila KO, Wasenius VM.

(9) http://ije.oxfordjournals.org/cgi/content/full/32/4/584  Cancer - Iodine deficiency, radiation dose, and the risk of thyroid cancer among children and adolescents in the Bryansk region of Russia following the Chernobyl power station accident by V Shakhtarin et al.

(10) http://www.ncbi.nlm.nih.gov/pubmed/12762644  Influence of iodine deficiency and iodine prophylaxis on thyroid cancer histotypes and incidence in endemic goiter area. Huszno B, Szybinski Z, Przybylik-Mazurek E, Stachura J, Trofimiuk M, Buziak-Bereza M, Golkowski F, Pantoflinski J.

(11) http://www.ncbi.nlm.nih.gov/pubmed/9349576  Thyroid. 1997 Oct;7(5):733-41. Incidence and clinical characteristics of thyroid carcinoma after iodine prophylaxis in an endemic goiter country. Bacher-Stier C et al.

(12) http://findarticles.com/p/articles/mi_m0FDN/is_2_13/ai_n27943644 / Iodine: deficiency and therapeutic considerations - Alternative Medicine Review, June, 2008 by Lyn Patrick

(13) http://www3.interscience.wiley.com/journal/112684400/abstract   The frequency of cold thyroid nodules and thyroid malignancies in patients from an iodine-deficient area  by Antonino Belfiore, MD

(14) http://www.ncbi.nlm.nih.gov/pubmed/17891233  Arq Bras Endocrinol Metab vol.51 no.5 São Paulo July 2007. Relevance of iodine intake as a reputed predisposing factor for thyroid cancer

(15) http://www.ncbi.nlm.nih.gov/pubmed/18018554  Nippon Rinsho. 2007 Nov;65(11):1953-8. Epidemiology of thyroid tumors: effect of environmental iodine intake.  Kasagi K. et al.

(16) http://www.ncbi.nlm.nih.gov/pubmed/19655332  Laryngoscope. 2009 Aug 4. Survival impact of treatment options for papillary microcarcinoma of the thyroid.  Lin HW, Bhattacharyya N.

(17) http://www.endocrine-abstracts.org/ea/0016/ea0016P685.htm  Endocrine Abstracts (2008) 16 P685 European Congress of Endocrinology 2008 Berlin, Germany 03 May 2008 - 07 May 2008.  Neither total thyroidectomy nor radioiodine remnant ablation improved long-term outcome in 900 patients with papillary thyroid microcarcinoma treated during 1945 through 2004. Ian Hay, Maeve Hutchinson, Megan Reinalda, Clive Grant, Bryan McIver & Geoffrey Thompson. Mayo Clinic, Rochester, Minnesota, USA.

(18) http://www.cancernetwork.com/cme/article/10165/1421632  June 11, 2009 ONCOLOGY. Vol. 23 No. 7 Areas of Confusion in Oncology . What Is the Optimal Initial Treatment of Low-Risk Papillary Thyroid Cancer (and Why Is It Controversial)? Ernest L. Mazzaferri, MD, MACP

(19) http://emedicine.medscape.com/article/849000-overview   Papillary thyroid carcinoma

(20) http://www.medscape.com/viewarticle/707327  Radioiodine for Most Papillary Thyroid Cancers Is Overtreatment, Says Expert, Zosia Chustecka Medscape Today

(21) http://cancerology.blogspot.com/2009/08/radioiodine-probably-overtreatment-for.html  RADIOIODINE PROBABLY OVERTREATMENT FOR MOST THYROID CANCER PATIENTS

(22) http://www.bmj.com/cgi/eletters/338/mar13_1/b733#210607   Radiological and Cytological Burden, Dr Steve Colley, reply to Investigating the thyroid nodule by H M Mehanna,

(23)  http://www.redorbit.com/news/science/34848/renaming_papillary_microcarcinoma_of_the_thyroid_gland_the_porto_proposal/  Renaming papillary microcarcinoma of the thyroid gland: The Porto proposal.

(24) http://ijs.sagepub.com/content/11/4/249.extract Renaming Papillary Microcarcinoma of the Thyroid Gland: The Porto Proposal. Rosai et al. Int J Surg Pathol.2003; 11: 249-251 .

(25) http://www.annals.org/cgi/content/full/126/3/226   Thyroid Incidentalomas: Management Approaches to Nonpalpable Nodules Discovered Incidentally on Thyroid Imaging  Gerry H. Tan, MD, and Hossein Gharib, MD  Annals of Internal Medicine  February 1,  1997, Volume 126, Issue 3, Pages 226-231

(26) http://www.ncbi.nlm.nih.gov/pubmed/12804106  Thyroid. 2003 Apr;13(4):381-7 .  An observation trial without surgical treatment in patients with papillary microcarcinoma of the thyroid. Ito Y, Uruno T, Nakano K, Takamura Y, Miya A, Kobayashi K, Yokozawa T, Matsuzuka F, Kuma S, Kuma K, Miyauchi A.

(27) http://www.ncbi.nlm.nih.gov/pubmed/15490053  World J Surg. 2004 Nov;28(11):1115-21.  Papillary microcarcinoma of the thyroid: how should it be treated?  Ito Y et al.

(28) http://www.ncbi.nlm.nih.gov/pubmed/17465240   Anticancer Res. 2007 Mar-Apr;27(2):1039-43.  Long-term follow-up for patients with papillary thyroid carcinoma treated as benign nodules. Ito Y et al.

(29) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1770442  J Clin Pathol. 2004 October; 57(10): 1041–1046.  Papillary carcinoma of the thyroid in Japan: subclassification of common type and identification of low risk group - K Kakudo,1 W Tang,1 Y Ito et al.

(30) http://www.jpgmonline.com/article.asp?issn=0022-3859;year=2007;volume=53;issue=1;spage=23;epage=26;aulast=Sakorafas . PGM 2007 ,  Volume : 53 ,  Issue : 1,  Page : 23-26, Post Graduate Medicine. Microscopic papillary thyroid cancer as an incidental finding in patients treated surgically for presumably benign thyroid disease.  GH Sakorafas et al.

(31) http://www.ncbi.nlm.nih.gov/pubmed/17786355   Comparative genomic hybridization, BRAF, RAS, RET, and oligo-array analysis in aneuploid papillary thyroid carcinomas.  Rodrigues R et al.

(32) http://www.ncbi.nlm.nih.gov/pubmed/15880523  Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Quiros RM, Ding HG, Gattuso P, Prinz RA, Xu X. Department of General Surgery, Rush University Medical Center, Chicago, Illinois 60612, USA.

(33) http://www.springerlink.com/content/unl9e830025jrlwa/   Anaplastic Thyroid Carcinoma Survival . Petri E. Voutilainen1, Markku Multanen1, Reijo K. Haapiainen1, Ari K. Leppäniemi1 and Arto H. Sivula1  Second Department of Surgery, Helsinki University Central Hospital, Box 260, FIN-00029 HUCH, Helsinki, Finland, FI

(34) http://www.ncbi.nlm.nih.gov/pubmed/11742333  Surgery. 2001 Dec;130(6):1028-34. Anaplastic thyroid carcinoma: a 50-year experience at a single institution.  McIver B, Hay ID, Giuffrida DF, Dvorak CE, Grant CS, Thompson GB, van Heerden JA, Goellner JR. Department of Medicine, Mayo Clinic & Foundation, Rochester, MN 55905, USA.

(35) http://www.thyroid.org/professionals/publications/news/07_10_05_kuffner.html    ATA News Release 2007.  Small Papillary Thyroid Cancer Is More Common and Not Without Risk than Previously Believed

(36) http://thyroid.about.com/od/thyroidcancer/a/microcarcinoma.htm   Papillary Thyroid Microcarcinoma -Do Total Thyroidectomy and/or Postoperative Radioiodine Improve the Outcome? By Mary Shomon, About.com Updated: May 09, 2008

(37) http://www.bcm.edu/oto/grand/12_04_03.htm  Papillary Thyroid Carcinoma -Grand Rounds Christopher Prichard, M.D. December 4, 2003

(38) http://www.snm.org/index.cfm?PageID=6730&RPID=7320  September 11, 2007 Thyroid Cancer Treatment May Be Overly Aggressive Reuters Health

(39) http://www.ncbi.nlm.nih.gov/pubmed/16780882   J Surg Res. 2006 Aug;134(2):160-2. Epub 2006 Jun 14. What is the biology and optimal treatment for papillary microcarcinoma of the thyroid? Cheema Y, Olson S, Elson D, Chen H.

(40) http://www.ncbi.nlm.nih.gov/pubmed/18035964  Expert Opin Pharmacother. 2007 Dec;8(18):3205-15. Appropriate treatment for asymptomatic papillary microcarcinoma of the thyroid. Ito Y

(41) http://www.ncbi.nlm.nih.gov/pubmed/17315032?   Nat Clin Pract Endocrinol Metab. 2007 Mar;3(3):240-8. A therapeutic strategy for incidentally detected papillary microcarcinoma of the thyroid. Ito Y, Miyauchi A.Department of Surgery, Kuma Hospital, Kobe, Japan.

(42) http://www.trnres.com/ebook/uploads/itocontents.pdf  Recent Advances in Thyroid Cancer Research 2006 Editors Yasuhiro Ito Akira Miyauchi Nobuyuki

(43) http://www.springerlink.com/content/uuecjwpd8tdgmxq8/fulltext.pdf?page=1  Preoperative Ultrasonographic Examination for Lymph Node Metastasis: Usefulness when Designing Lymph Node Dissection for Papillary Microcarcinoma of the Thyroid .  Yasuhiro Ito  April 2004

(44) http://www.springerlink.com/content/6khwgm0h98wh2h0h/   Papillary Microcarcinoma of the Thyroid: How Should It Be Treated?   Yasuhiro Ito   Department of Surgery, Kuma Hospital, 8-2-35 Shimoyamate-dori, Chuo-ku, 650-0011 Kobe City, Japan  October 2004

(45) http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=502418  J Clin Pathol. 1991 March; 44(3): 205–207.  Occult papillary microcarcinoma of the thyroid--a potential pitfall of fine needle aspiration cytology? H R Harach, E Saravia Day, and S B Zusman

(46) http://www.ncbi.nlm.nih.gov/pubmed/15395984  J Clin Endocrinol Metab. 1949 Nov;9(11):1216-31. Nonencapsulated sclerosing tumors of the thyroid.  Hazard JB, et al.

Author Jeffrey Dach MD