Vol.2, No.5, 391-394 (2010) Health
Copyright © 2010 SciRes. Openly accessible at http://www. scirp.org/journal/HEALTH/
Concurrent pulmonary Mycobacterium avium complex
(MAC) infection and active Hürthle cell thyroid
carcinoma: is there a connection?
Kara M. Meinke Baehr, Whitney S. Goldner*
University of Nebraska Medical Center, Department of Internal Medicine–Diabetes, Endocrinology, and Metabolism, Omaha, USA
*Corresponding Author: wgoldner@unmc.edu
Received 5 October 2009; revised 5 January 2010; accepted 8 January 2010.
We present two cases of pulmonary MAC infec-
tion in women with Hürthle cell thyroid carci-
noma. Both cases were asymptomatic octoge-
narian women with active Hürthle cell thyroid
carcinoma and prolonged periods of hypothy-
roidism prior to diagnosis of pulmonary MAC.
Mycobacterium avium complex has never been
reported in association with any type of thyroid
cancer, specifically Hürthle cell carcinoma. A
review of the literature and possible associa-
tions between the two are discussed in this ar-
Keywords: Hürthle Cell Thyroid Cancer;
Hypothyroidism; Mycobacterium Avium Complex;
Cellular Immunity
Hürthle cell thyroid carcinomas are a type of
well-differentiated thyroid carcinoma and are either
classified as a subset of follicular carcinoma or a sepa-
rate category of well-differentiated thyroid cancer [1].
Hürthle cell carcinomas usually produce thyroglobulin,
but are often less iodine avid, and are more aggressive
than the other types of well-differentiated thyroid carci-
noma such as papillary or follicular [2,3]. There is a fe-
male predominance with peak ages of incidence in the
seventh and eighth decades [2]. Specific treatment is
controversial, but generally total thyroidectomy and
remnant ablation is recommended [1]. Follow-up for
Hürthle cell thyroid cancer is similar to papillary and
follicular thyroid cancers, which entails anatomic imag-
ing of the neck and chest. This is usually done with neck
ultrasound and computed tomography (CT) scans of the
chest and occasionally neck; and when indicated,
TSH-stimulated I-131 whole body scan is performed.
Laboratory follow- up includes tumor marker evaluation
with serum thyroglobulin (Tg) and antibodies. Thyroid
hormone suppression is also a mainstay of therapy. De-
spite its more aggressive course, there are no known
associations between Hürthle cell thyroid cancer and
immunocompromised states; specifically, there are no
published reports of Hürthle cell thyroid carcinoma and
pulmonary MAC infection.
MAC refers to mycobacterium infections caused by
free-living nontuberculous organisms that are inhaled or
ingested from the environment [4]. Among nontubercu-
lous species, MAC is the most common cause of pul-
monary disease in the United States. Diagnosis of pul-
monary MAC requires both imaging consistent with
pulmonary disease and microbiologic confirmation in a
symptomatic patient to necessitate treatment [4]. In-
creased rates of MAC in immunocompromised patients
with AIDS were reported in the 1990s; however, with
improved anti-retroviral therapies, MAC infections in
HIV infected patients have been declining [5]. The in-
creased susceptibility of patients with AIDS to dissemi-
nated nontuberculous mycobacteria infections helps pro-
vide insight into the pathogenesis of these infections in
non-immunocompromised hosts. Disseminated MAC
infections usually occur when the CD4+ T-lymphocyte
count is < 50 µl, suggesting that some intrinsic activity
of the T-lymphocytes is important for immunity to my-
cobacteria [6]. We present two cases of pulmonary MAC
infection in octogenarian women with active Hürthle cell
thyroid carcinoma.
2. CASE 1
Case 1 is a 79 year-old female initially diagnosed with
stage 2 Hürthle cell carcinoma (pathologic stage T2N0M0)
in February 1999. She underwent total thyroidectomy
and remnant ablation with 100 mCi of I-131. Posttreat-
ment scan showed uptake in the central neck consistent
with thyroid remnant without evidence of local or distant
K. M. M. Baehr et al. / HEALTH 2 (2010) 391-394
Copyright © 2010 SciRes. Openly accessible at http://www. scirp.org/journal/HEALTH/
metastases. She had no follow-up until 2006 when she
presented to our institution for evaluation of multiple
pulmonary nodules. Excisional biopsy of one of the le-
sions was consistent with metastatic Hürthle cell carci-
noma. Thyroid ultrasound showed no evidence of thy-
roid cancer in the neck. Thyroglobulin (Tg) was 136
ng/mL (goal < 0.1 ng/ml in remission) with negative anti-
thyroglobulin antibodies, and thyroid stimulating hor-
mone (TSH) of 11.5 mcIU/mL. I-123 whole body scan
showed uptake in the thyroid bed and superior medi-
astinum and stimulated Tg was 155 ng/mL. She under-
went repeat radioactive iodine ablation with 206 mCi of
I-131 using dosimetry to calculate her dose. Her post-
treatment scan showed heterogeneous uptake throughout
the lungs, most intense in the left lower lobe, and uptake
in the thyroid bed.
Despite successful uptake on radioactive iodine scans,
six months after treatment, Tg had risen to 341 ng/mL.
Repeat chest CT was unchanged. PET scan showed up-
take in the right middle lobe pulmonary nodule and bi-
lateral lower lobe lesions that were calcified with lower
SUVs suggesting more benign disease. Since most of the
pulmonary lesions were not PET avid, indicating they
were likely radioiodine avid, she received another 249.6
mCi of I-131 with dosimetry in March 2008. Post-
treatment scan showed faint uptake throughout the lungs
bilaterally, but no uptake to correspond with the largest
pulmonary nodules, suggesting the pulmonary metasta-
ses were no longer radioiodine avid. Following treatment,
Tg continued to rise and was 3976 ng/mL in July 2008
on thyroid hormone suppression. Follow-up chest CT
showed numerous pulmonary nodules, two lesions in-
creased in size in the right upper lobe, along with scat-
tered tree-in-bud opacities, bronchial wall thickening,
and bronchiectasis suggesting mycobacterium avium
complex (MAC). Induced sputum was culture positive
for MAC. The patient was referred to infectious disease
and no treatment was recommended since she was as-
A PET scan showed disease progression within the
mediastinum and right hilum with a maximum SUV of
12.4 in a subcarinal mass and multiple PET avid pulmo-
nary nodules. The hilar mass was felt to be
non-resectable, so she was treated with external beam
radiation therapy for her mediastinal mass and sensitiz-
ing chemotherapy with doxorubicin in November 2008.
After starting chemotherapy, she developed worsening
productive cough, chills, and fatigue and significant
oxygen desaturation. Since MAC was still present in her
sputum, she was started on triple antibiotic therapy
(azithromycin 500 mg daily, rifampin 300 mg daily, and
ethambutol 800 mg daily) for her symptomatic MAC in
January 2009. She has symptomatically improved and no
longer has a productive cough; however, continues to
require supplemental oxygen. Her most recent Tg was
1582 ng/ml (down from maximum 3976 ng/ml) with
negative antibodies and a TSH of 0.45 mcIU/ml. Chest
CT shows interval decrease in bilateral consolidations,
unchanged bilateral bronchiectasis and 2 right lower
lobe nodules, and a decrease in the subcarinal lymph
node size.
3. CASE 2
Case 2 is an 82 year-old female diagnosed with stage 2
Hürthle cell carcinoma (T3N0M0) in July 2004 and un-
derwent total thyroidectomy and remnant ablation with
45.8 mCi of I-131. Post-treatment scan showed only
uptake in the thyroid bed. In September 2005, she un-
derwent a TSH-stimulated (with thyrogen) whole body
scan that showed 1.6% minimal uptake in the area of the
thyroid bed. Tg stimulated to 0.2 ng/ml with a TSH of
315 mcIU/mL. She refused additional radioactive iodine
therapy due to severe sialoadenitis with the first treat-
ment. Thyroid ultrasound revealed residual thyroid tis-
sue in the right bed measuring 1.2 × 0.7 × 1.1 cm and no
evidence of focal nodules or lymphadenopathy.
Repeat thyroid ultrasounds in September 2006 and
August 2007 showed no evidence of recurrence. Tg level
ranged 0.3-0.8 ng/ml, antibodies remained negative, and
TSH ranged from undetectable to 3.6 mcIU/ml during
this time. Tg increased to 2.9 ng/mL in March 2008 with
an elevated TSH of 31.5 mcIU/ml; however, decreased
to 1.7 ng/mL in August 2008 (TSH 6.9 mcIU/ml) and
further to 1.5 ng/mL with a TSH of 0.14 mcIU/ml one
month later. Thyroid ultrasound in August 2008 showed
minimal right-sided residual thyroid tissue measuring
0.4 × 0.6 × 0.7 cm. Non-contrast chest CT showed a
right upper lobe semi-solid nodule measuring 1cm that
was suspicious for cancer. CT also revealed bronchiecta-
sis changes in anterior portions suspicious for MAC; and
her induced sputum was MAC culture positive. PET
scan was normal. After infectious disease consultation,
she was not treated for her MAC because she was as-
Follow-up chest CT in February 2009 showed stable
mixed solid and ground glass nodules in the right upper
lobe, bilateral patchy consolidations, and an enlarging
precarinal lymph node. This lymph node was biopsied
and pathology was negative for malignancy. Tg has con-
tinued to increase and is currently 8.4 ng/ml in August
2009, and TSH is 0.087 mcIU/ml. She is still asympto-
These cases are the first to report pulmonary MAC in-
fection in persons with active Hürthle cell thyroid carci-
noma. Interestingly, both these patients were asympto-
matic, octogenarian women and diagnosis was initially
suggested by radiographic findings and later confirmed
K. M. M. Baehr et al. / HEALTH 2 (2010) 391-394
Copyright © 2010 SciRes. Openly accessible at http://www. scirp.org/journal/HEALTH/
with culture positive induced sputum. Typical radiologic
findings consistent with pulmonary MAC infection on
chest radiographs or computed tomography (CT) include
nodular infiltrates, multifocal bronchiectasis, cavitation,
and multiple small nodules [7]. The nodules and bron-
chiectasis are usually present within the same lobe and
occur most frequently in the right middle lobe and lin-
gula [8,9]. The keys to our patient’s diagnoses were the
presence of new, non-dependent bronchiectasis that was
different from the other pulmonary disease previously
seen on past CT scans.
Four different clinical syndromes of pulmonary MAC
infection have been described. These include classic
cavitary disease seen commonly in middle-aged smoking
males [6]; nonclassic forms such as bronchiectasis and
multiple nodules found in elderly women [6,8], MAC
lung disease in cystic fibrosis patients [10], and a hyper-
sensitivity pneumonitis associated with hot tub use [11].
The clinical syndrome that is most likely in our two
cases includes the group who presents with mid-lung
nodular bronchiectasis with multiple nodules and
tree-in-bud opacities due to MAC with no underlying
lung disease or immunosuppression. This bronchiectatic
form of the disease is frequently termed the “Lady Win-
dermere syndrome” and presents in slender, middle-aged
to elderly Caucasian women and involves the right mid-
dle lobe and/or lingula [6,12]. The first report of this
form of MAC cites 21 such patients, most non-smoking
women with a mean age of 66 years, who presented with
symptoms of persistent cough and purulent sputum [13].
This group is homogeneous, consisting of older, Cauca-
sian, otherwise healthy women, raising the possibility of
a host defense immune defect to explain disease suscep-
tibility [14]. Whereas mutations in the interferon-gamma
and interleukin-12 production and response pathway
have been proposed, no consistent immune phenotype in
pulmonary nontuberculous mycobacteria infection has
been clearly established [15]. Both of our patients were
Caucasian women in their late 70’s and early 80’s with
Hürthle cell thyroid carcinoma and no obvious form of
immunosuppression; however, they were both asymp-
tomatic which is in contrast to how the Lady Winder-
mere syndrome group usually present. There are no
studies linking thyroid cancer or its treatment with im-
munosuppression. However, Hürthle cell thyroid carci-
noma often has a more aggressive course than papillary
or follicular thyroid carcinoma [12] and tends to occur
more frequently in older women [2]. Case 1 had pulmo-
nary disease from her metastatic Hürthle cell carcinoma,
and case 2 had a pulmonary nodule, not definitively me-
tastatic thyroid cancer, so neither of the patients was
completely devoid of lung disease as described in the
Lady Windermere form of MAC pulmonary infection.
Another common feature for both cases was a pro-
longed period of hypothyroidism evidenced by an in-
creased TSH prior to diagnosis of MAC. Case 1 was
iatrogenically hypothyroid prior to both treatments with
radioactive iodine ablation using dosimetry in April
2007 and March 2008. Case 2 was hypothyroid due to
medication non-adherence from March through August
2008 which immediately preceded the diagnosis of pul-
monary MAC infection on chest CT. Animal studies
have shown a decrease in lymphocyte function during
hypothyroidism, with a return of normal lymphocyte
function during euthyroid states [16]. The number of
peripheral white blood cells, mainly lymphocytes, in
hypothyroid (thyroidectomized) animals is reduced to
half of normal levels [17]. Other studies have shown
dysregulation of CD4+ T lymphocyte responsiveness in
hypothyroid dogs suggesting a relationship between hy-
pothyroidism and cellular immunity [18]. Unfortunately
specific studies regarding cellular immunity in hypothy-
roid humans are lacking. Radioactive iodine treatment
can cause bone marrow suppression after treatment;
however, this happens in all types of thyroid cancer, not
exclusively Hürthle cell carcinoma, making it a less
likely etiology [19]. Given both women experienced
prolonged hypothyroidism immediately prior to their
diagnosis of MAC, we propose that the prolonged hypo-
thyroidism may have predisposed to suppression of
cell-mediated immunity in an already vulnerable host
(older, Caucasian women with potential lung pathology).
This may have resulted in both patients having an in-
creased susceptibility to acquire pulmonary MAC infec-
tion. There are no reports of altered immune function
associated with any thyroid carcinomas, and specifically
none that associate Hürthle cell thyroid carcinoma with
altered immune function; however, this is also a poten-
tial mechanism, especially given Hürthle cell thyroid
carcinoma often has a more aggressive course, and
should be considered and evaluated further. Also, ra-
diologic detection of MAC may be more common in
patients with more aggressive thyroid cancer due to
close monitoring of disease done by performing more
frequent radiographic scans.
To our knowledge, pulmonary MAC has not previously
been reported in association with any type of thyroid
cancer. We present two interesting cases of octogenarian
women with active Hürthle cell thyroid carcinoma who
developed pulmonary MAC infection after prolonged
periods of hypothyroidism. Further observations and
studies are necessary to understand the potential rela-
tionship between the two diseases.
[1] Watson, R., Brennan, M., Goellner, J., et al. (1984) Inva-
sive Hürthle cell carcinoma of the thyroid: Natural his-
K. M. M. Baehr et al. / HEALTH 2 (2010) 391-394
Copyright © 2010 SciRes. Openly accessible at http://www. scirp.org/journal/HEALTH/
tory and management. Mayo Clinic Proceedings, 59(12),
[2] Grossman, R. and Clark, O. (1977) Hürthle cell carci-
noma. Cancer Control, 4, 13-17.
[3] Yutan, E. and Clark, O. (2001) Hürthle cell carcinoma.
Current Treatment Options in Oncology, 2(4), 331-335.
[4] Good, R. and Snider, D. (1982) Isolation of nontubercu-
lous mycobacteria in the United States. Journal of Infec-
tious Diseases, 146(6), 829-833.
[5] Pallella, F. Jr., Delaney, K., Moorman, A., et al. (1998)
Declining morbidity and mortality among patients with
advanced human immunodeficiency virus infection. HIV
outpatient study investigators. New England Journal of
Medicine, 338(13), 853-860.
[6] Parrish, S., Myers, J. and Lazarus, A. (2008) Nontuber-
culous mycobacterial pulmonary infections in non-HIV
patients. Postgraduate Medicine, 120(4), 78-86.
[7] Erasmus, J., McAdams, H., Farrell, M. and Patz, E. Jr.
(1999) Pulmonary nontuberculous mycobacterial infec-
tion: Radiologic manifestations. Radiographics, 19(6),
[8] Levin, D. (2002) Radiology of pulmonary Mycobacte-
rium avium-intracellulare complex. Clinics in Chest
Medicine, 23(3), 603-612.
[9] Koh, W., Lee, K., Kwon, O., Jeong, Y., et al. (2005) Bi-
lateral bronchiectasis and bronchiolitis at thin-section CT:
Diagnostic implications in nontuberculous mycobacterial
pulmonary infection. Radiology, 235(1), 282-288.
[10] Olivier, K., Weber, D., Lee, J., et al. (2003) Nontubercu-
lous mycobacteria I: Multicenter prevalence study in
cystic fibrosis. American Journal of Respiratory and
Critical Care Medicine, 167(6), 828-834.
[11] Hartman, T., Jensen, E., Tazelaar, H., Hanak, V. and Ryu,
J. (2007) CT findings of granulomatous pneumonitis
secondary to Mycobacterium avium-intracellulare inha-
lation: “Hot tub lung.” American Journal of Roentgenol-
ogy, 188(4), 1050-1053.
[12] Reich, J. and Johnson, R. (1992) Mycobacterium avium
complex pulmonary disease presenting as an isolated
lingular or middle lobe pattern: The Lady Windermere
syndrome. Chest, 101(6), 1605-1609.
[13] Prince, D., Peterson, D., Steiner, R., et al. (1989) Infec-
tion with Mycobacterium avium complex in patients
without predisposing conditions. New England Journal
of Medicine, 321(13), 863-868.
[14] Huang, J., Kao, P., Adi, V. and Ruoss, S. (1999) Myco-
bacterium avium-intracellulare pulmonary infection in
HIV-negative patients without preexisting lung disease.
Chest, 115(4), 1033-1040.
[15] Kim, R., Greenberg, D., Ehrmantraut, M., et al. (2008)
Pulmonary nontuberculous mycobacterial disease. Ame-
rican Journal of Respiratory and Critical Care Medicine,
178(10), 1066-1074.
[16] Schoenfeld, P., Myers, J., Myers, L. and LaRocque, J.
(1995) Suppression of cell-mediated immunity in hypo-
thyroidism. Southern Medical Journal, 88(3), 347-349.
[17] Fabris, N. (1973) Immunodepression in thyroid-deprived
animals. Clinical & Experimental Immunology, 15(4),
[18] Tani, H., Nabetani, T., Sasai, K. and Baba, E. (2005)
Proliferative responses to canine thyroglobulin of pe-
ripheral blood mononuclear cells from hypothyroid dogs.
Journal of Veterinary Medical Science, 67(4), 363-368.
[19] Mazzaferri, E. and Kloos, R. (2001) Current approaches
to primary therapy for papillary and follicular cancer.
Journal of Clinical Endocrinology & Metabolism, 86(4),