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LIST OF TOPICS IN ORDER OF PRESENTATION BELOW---CLICK
ADD RECOMBINANT TSH TO ENDOGENOUS TSH FOR ABLATION?
AMIODARONE INDUCED THYROTOXICOSIS
What condition does this person suffer from?
T4 Suppression Therapy Post Radiation Exposure
MANAGING HASHIMOTO,S IN PREGNANCY
INFANT WITH CHYLOTHORAX AND APPARENT HYPOTHYROIDISM
WHAT TO DO WITH AN INCIDENTAL 1MM PAPILLARY CANCER?
INFANT WITH CHYLOTHORAX AND APPARENT HYPOTHYROIDISM
THERAPY OF THYROID CANCER WITH KNOW POSITIVE NECK NODES, ELEVATED TG,
AND NEGATIVE SCAN? 1 Nov 02
TRANSIENT HYPOTHYROIDISM, AND AN ELEVATED RAIU
IS THIS GRAVES’
DISEASE? 1 Oct 02
QUESTION- WHEN IS A PENTAGASTRIN TEST ADVISED IN FOLLOWING
How to manage existing hypothyroidism perioperatively in a patient NPO ?
QUESTION- HOW LONG TO WAIT AFTER OPERATION BEFORE RAI
DO WE REALLY NEED TO DO BOTH fT4 AND TSH IN
HOW TO TREAT SUB-CLINICAL HYPOTHYROIDISM?
HOW TO MANAGE
FETAL HYPOTHYROIDISM AND GOITER
ADD RECOMBINANT TSH TO ENDOGENOUS TSH FOR ABLATION?
I am a family physician in Toronto,
Ontario. I am also unfortunately the patient. I will be undergoing I131
treatment following my near total thyroidectomy last month for a
mulitcentric follicular variant papillary thyroid carcinoma. It was
completely resected. The primary nodule was 2.4 cm with capsular invasion
nut no extrathyroidal spread and no blood or lymphatic spread noted. In
the contralateral lobe there were two microfoci noted. My stsh currently
is around 80 and rising. My endocrinologist has suggested that using rtsh
prior to I131 will give a better result. What stsh level is usually aimed
for, and what dose of I131 would you use. Given my age (37), the size of
the tumour, and its multicentricity, it has been suggested that 150 mCu of
I131 was appropriate, but from what I have read, it would seem that most
people are using lower doses.Thanks. (Name lost in Webspace!)
RESPONSE- I feel that your TSH is high enough
for a successful ablation of any thyroid remnant. I don't see the need for
adding recombinant human TSH. In our experience the addition of endogenous
and exogenous TSH does not result in additional advantages over endogenous
TSH alone. Regarding the dose, 100 mCi is usually effective (nearly 90% of
the cases) and even lower doses such as 30 mCi have been associated with
successful ablation in 80% of the cases.Sincerely, F. Pacini MD
AMIODARONE INDUCED THYROTOXICOSIS (10 Feb 203)
I am a 67year old cardiologist. I recently had a succesful pulmonary vein
ablation for paroxysmal AF. Prior to the ablation I ceased taking
Amiodarone which had been administered for two years. Approximately 6
weeks after stopping Amiodarone I had lost 14kg in weight and had a
tremor and heat intolerance and other symptoms. TFTs were TSH <0.02, T4
46 and T3 20. These are now (7weeks later) almost normal.
Is the thyrotoxicosis related to the Amiodarone?
Other findings:Increased mucus in the throat plus cough.,Minor dysphagia,
Decreased libido, These have receded with the normalisation
of the TFTs. Could they be related to thyrotoxicosis?
Initially it was noted that I had a mild normochromic anemia(118) and a
neutropenia which was thought to be due to the Carbimazole I was taking.
However on checking all the blood results it was found that both these
values had been recorded on two occasions before the Carbimazole was
commenced. Are anemia and neutropenia associated with thyrotoxicosis?
I look forward to your comments. Ian E Langbein, MD.
RESPONSE-Amiodarone may indeed cause thyrotoxicosis. Amiodarone
induced thyrotoxicosis (AIT), may occur early after taking the drug,
during usage for several years and even (long time) after with-drawl of
the drug because it is stored in tissues and slowly released from
them.There are 2 ways of induction of thyrotoxicosis:
- AIT type I: this type is caused by the load of iodine load released
from Amiodarone leading to increased thyroid hormone synthesis. The
exact mechanism is obscure in that it is not known why contra
regulatory mechanisms such as inhibition of uptake and/or
organification do not operate sufficiently. Type I may occur in
thyroids with pre-existing thyroid disorder like thyroid autoimmunity
or nodularity but not necessarily so. The drug contains about 37%
iodine by weight. A daily Amiodarone dosage between 200 and 600 mg
releases a 50 to 100 fold iodine excess compared to the optimal iodine
intake between 150 to 200 µg per day. In patients living in areas of
iodine deficiency, RAI
uptake of the thyroid gland is often inappropriately elevated despite
the iodine load, but always low when iodine intake is normal. In AIT
type I, serum interleukine 6 (IL-6), is normal or only slightly
elevated indicating that thyroid destruction is not prominent in this
sub type of AIT (see below). Color flow Doppler
sonography shows hypervascularity as is seen in
’’ disease. Treatment starts with administration of methimazole 40
to 60 mg daily, or propylthiouracil 600 to 800 mg daily to inhibit
thyroid hormone synthesis, and perchlorate 1 gram daily, to inhibit
iodine entry in thyroid cells. Both the serum IL-6 levels and
sonographic findings are useful to distinguish AIT type I from type
II, see below.
- AIT type II, is caused quite differently in that Amiodarone
induces destructive thyroiditis. This destruction is both
caused by the drug itself and by the released iodine. Because of the
damage to the thyroid cells, stored thyroid hormone is released into
the circulation causing the thyrotoxicosis. Contrary to type I, IL-6
levels are elevated and color flow Doppler sonography does not show
increased vascularity. Treatment consists of administration of
glucocorticoids, such as prednisone. Sometimes mixed forms of type I and II are encountered and both
treatment modalities should be applied together.
Further answers to your questions: Amiodarone really
has very many different side effects and I would not be surprised as the
ones you mention are also due to the drug and/or the thyrotoxicosis
itself. Throtoxicosis may indeed cause normochromic anemia and
neutropenia.Further reading: Bogazzi et al. Thyroid 11, 511-519, 2001 .
Georg Hennemann, MD, PhD
At 07:46 AM 2/3/03 -0600, you wrote:
What condition does this person suffer from?>
HISTORY: Mrs. M is an 87-year-old woman who is referred for treatment of
hyperthyroidism. The patient was recently admitted to our institution for
chest pain and shortness of breath resulting from CHF. During evaluation
of this illness, the patient had thyroid function studies drawn (see
laboratory section below). The patient gives a history of fluctuating weight
associated with a decreased appetite, intermittent cold intolerance,
intermittent constipation, decreased energy level, and a mild tremor. She does not
complain of perspiration, hair loss, eye problems, goiter, or anterior neck
pain. She states that she has not had previous irradiation to the neck or
face or I-131 therapy. She gives no family history of thyroid disorders.
Her current medications are metoprolol, Prevacid, subcutaneous heparin,
enalaprilat, aspirin, and a sliding scale regular Insulin. She denies any
recent oral or intravenous radiocontrast or other exogenous sources of iodine
such as health food supplements or medications.
PHYSICAL FINDINGS: The patient's blood pressure is 102/58 mm Hg. Heart
rate is 102/minute. Examination of the head reveals no proptosis or lid lag.
The thyroid is approximately 40 grams; there is
no dominant nodularity, no bruit, or thrill overlying the thyroid. It is
non-tender, and there is no associated lymphadenopathy. The heart is
regular, but tachycardic; she has a 3/6 systolic ejection murmur. The lungs
reveal minimal basilar crackles bilaterally. There is 2+ lower extremity
edema. Neurologically, there is a mild distal tremor; the deep tendon reflexes
are 2/4 without delay.
LABORATORY FINDINGS: On the day she was admitted for CHF her TSH was 0.04
range 0.4-6.2). Two days later the free T4 was 1.5 ng/dl (0.7-1.8), and
the total T3 was 46.6 ng/dl (45-132). Thyroid uptake of I-131 completed
three days after admission was 38% (normal range 10-30%). Her Blood Urea
Nitrogen was 48 mg/dl (8-25) and Creatinine 3.0 mg/dl (0.6-1.5).
Is she hyperthyroid?
Is she sick euthyroid?
Does she have central hypothyroidism?
Confounding factors: ? subcutaneous heparin falsely elevating FT4; ? renal
insufficiency falsely elevating I-131 uptake.
Thanks for your help in advance, Mike DeRosa, Endocrine Fellow, Washington University School of Medicine,
RESPONSE-Obviously the diagnosis is uncertain, or you would not be writing! However, she probably has an element of "Non-thyroidal illness syndrome", plus effects of renal failure,
ASA, and maybe background thyrotoxicosis. Heparin can raise the free T4 by dialysis, but I
do not think it would effect the test you do, which is probably a one-tube lab assay, not dialysis. ASA will lower her T4 and FT4
especially if the dose is .6gm/day or up. Renal failure usually causes a lower RAIU since there is retention of iodine, but if the changes are acute, it might produce a different effect.
NTIS, which is probably central hypothyroidism, could explain her TSH, and blood tests, but not the
RAIU. Also the TSH is lower than usually seen in NTIS. It would be of interest to add anti-thyroid antibodies, and to do a thyroid US, thinking of the Graves/Toxic MNG differential diagnosis.
I believe that currently she is not toxic, because it is hard to conceive that someone
with a T3 of 46 can be toxic. However I also suspect that she may have hyperthyroidism which will emerge if and when she recovers from her acute
illness. I will ask other members of our editorial group to comment on your
case and add their remarks if substantially different.
L De Groot, MD
PS- A poll of THYROIDMANAGER editors found most supported the diagnosis of
NTIS as the main problem, with agreement that thyrotoxicosis could be
present but masked. LD
T4 Suppression Therapy Post Radiation Exposure
A 65 year old white female with history of irradiation as an infant, apparently as a treatment for an enlarged thymus. The patient has been on T4 suppression therapy since age 20.
Thyroid function tests show normal T4 and suppressed TSH, compatible with her treatment goals. Thyroid gland is non-palpable and the latest thyroid ultrasound done three months
ago showed no evidence of thyroid nodules. The patient otherwise is asymptomatic, with no history of documented osteoporosis and no history of atrial fibrillation.
Should this patient continue to be on T4 suppression therapy?
Thank you, and best regards. Ahmad A. Tarhini, MD,Internal Medicine Resident
University of Pittspurgh Medical Center,Mckeesport Hospital
RESPONSE-Your question is an excellent one, but there is no answer that is proven
to be correct. It is hard to believe that after nearly 60 years that a neoplasm could suddenly begin. One thinks more likely such mutational
events happen near the time of the radiation, and slowly grow over the years. The fact that her exam and US are normal is also supportive of
stopping treatment. Thus the risk of stopping medication must be very low, especially if you do a follow exam and US annually. On the other hand, if her heart and bones are perfect, and her TSH
is at the bottom end of normal ( not truly suppressed) below normal, it would also seem that the risk of continuing treatment in this patient is
negligible.I think I would finally end on the side of cautiously continuing
treatment, so long as there are no contraindications.
Leslie J De Groot,MD
MANAGING HASHIMOTO,S IN PREGNANCY
What are the current recommendations regarding > treating Hashimoto's
during pregnancy? How frequently should the woman be monitored
with thyroid tests? Should she be followed a high risk OBGYN?
Thank you. Dr. Amy Handler, Katonah, NY
RESPONSE- This question demands an answer subdivided in several parts.
Concerning thyroid function, most patients (but not all) with Hashimoto's
disease already take l-T4 before pregnancy (this was not specified in the
question asked). - If it is the case, thyroid function tests should be
carried out rapidly after conception (say, within 8-10 weeks and no later
than 12 wks) and the l-T4 dosage adapted. Depending on the functional
capabilities of the thyroid gland to adapt to the increased hormonal
demands during gestation (see article by Mike Kaplan in Thyroid), the
daily dosage should be increased (usually by 30-60 % eventually, above
preconception dosage), but it is important to note that the l-T4 increment
may vary widely individually. The main objective in these early stages is
to avoid a raise in serum TSH and obviously a fall in free T4 (risk for
the fetal development, etc). After this early adaptation, we check thyroid
function in such patients every 2 months until 5-6 months gestation.
Thereafter the dosage usually remains unchanged until parturition. - If
this Hashimoto patient does not yet require l-T4 before pregnancy because
she is euthyroid, I suggest to follow the algorithm that I have proposed
in 1998 (see Trends in Endocrinology & Metabolism, vol. 9; N° 10;
December 1998). In this scheme, we base our attitude on the titers of
thyroid antibodies and serum TSH levels (when these are still within
normal range) to decide whether to treat or monitor. If l-T4 treatment is
given, the buckle rejoins the first option discussed above. If l-T4
treatment is not warranted (TSH below 2.5 mU/L; low Ab titers; normal free
T4 around mid-gestation), we later monitor thyroid function tests (TSH and
free T4) around 27-28 and 34-35 weeks gestation. - An additional
difficulty could be those (extremely rare) patients who would only have a
low-normal free T4 without serum TSH elevation during early gestation. We
don't encounter such patients (but others do ??) and it has been proposed
by some authors to give the mother (and perhaps the fetus ?) the potential
benefit of l-T4 treatment in such instances. - In all cases patients with
Hashimoto's disease should see an endocrinologist during and after the
pregnancy (because of the risk of postpartum thyroiditis). During
pregnancy, we follow these patients in close collaboration with the ObGyn,
but high risk ObGyn is not mandatory (in my opinion). - It should also be
remembered that Hahimoto's patients have an increased risk of early
miscarriage (see article by Poppe et al. in Thyroid, November 2002 and a
review in press by Glinoer in Human Reproduction Update). This risk could
justify the opinion of a "high risk ObGyn", even though there is
not much that can presently be done to reduce the miscarriage risk (except
to have a normal thyroid function, probably ?); in rare cases trials have
been initiated using steroids or iv IG (in women with recurrent
Prof Daniel Glinoer
INFANT WITH CHYLOTHORAX AND APPARENT HYPOTHYROIDISM (11 Jan
I would be greatful for advice over management of this
case. A one month old girl with Down Syndrome was admitted in
the PICU due to respiratory distress 20 days ago and bilateral
chylothorax was diagnosed. Bilateral drainages tubes were placed and
fluid analysis confirmed chylothorax. Debt is more or less 500
ml/day and albumin fell to 2 g/dL. She has not any congenital
cardiac defect. Now she is on mechanic respiratory assistance
due to respiratory distress and she needs inotropic
support with dopamine and adrenaline. She does not look like
severe hypothyroidism. At neonatal screening TSH was 15, now TSH is
> 45 mU/l, FT4 0.6 ng/dl , T4 4.5 mcg/dl, T3 70 ng/dl.
Questions: Is she really hypothyroid? Is it only a
transport problem due to TBG or albumin leak or both, due to thyroid
hormone leak? We start LT4 replacement by nasogastric
tube (25 mcg/day), but how about LT4 transport to systemic
circulation. Is it by portal system or lymphatic route ?
Thanks in advance.
Guillermo Alonso, MD Pediatric Endocrinology, Hospital Italiano de Buenos
Response-Dr Alonso- The tests described to not clearly identify a
lack of TBG, since the drop in freeT4 and T4 are more or less equal.
However in this situation TBG is probably reduced along with other
proteins. It would be of interest to have the old-fashioned T3 Resin
uptake / T4 combination which would clarify that issue, or a direct
measure of TBG by RIA. I believe she is hypothyroid based on TSH and low
freeT4, but not terribly so because T3 is near bottom normal. The cause of
the hypothyroidism is not yet clear, but it is either primary thyroid
disease or loss of T4. Presumably she would need a TBG leak out of
the body to cause low TBG/T4, as in the nephrotic syndrome. I believe leak
into a chylothorax would initially be recirculated. However since this is
being drained each day, it may constitute a serious loss of thyroid
hormone. If your therapy is satisfactory her T4 should respond promptly to
the administered hormone, but if she is loosing much into the chylothorax
the dosage will need to be increased. Possibly the chylothorax is telling
you that something is aberrant in her gut, in which case absorption might
be a problem. So far as I know the absorption of T4 and T3 from the gut is
via the mesenteric vessels and portal vein. The dopamine may also be
worsening thyroid function by lowering TSH from an even higher level. Best
regards, Leslie J De Groot, MD
WHAT TO DO WITH AN INCIDENTAL 1MM PAPILLARY CANCER?16 Dec
What is the appropriate workup and treatment plan for a 41 yo
female who underwent right total thyroidectomy for what was
initially felt to be a single hot nodule with symptoms of
hoarseness, localized pain and enlargement? Path report
revealed 1 large encapsulated adenoma as well as several
smaller nodules. An incidental finding unrelated to any
nodule and without vascular involvement was a 1 mm papillary
carcinoma, follicular variant. Should this patient be
evaluated and treated as stage 1 papillary cancer with total
thyroidectomy plus minus RAI, with hormone suppression or should the
finding be considered incidental and followed annually?
Thank you. Mark J. Krzyston, MD, 1175 Cook Rd. Ste 225,
Orangeburg, SC 29118
RESPONSE-If the contralateral side was normal at operation and
normal by US, and careful review of pathology reveals no evidence of
malignancy in any of the nodules, I believe following the patient on T4
replacement with periodic US exams is sufficient. If the contralateral
side was abnormal at op or on US, the abnormality would have to be
evaluated independently "de novo" by appropriate studies such as
US and FNA. Tiny (1-4mm) papillary cancer foci are found in 6% or more of
autopsy series, and clearly in most cases carry a benign prognosis. But
there are occasional reports of metastases from tiny primary foci, and
obviously larger tumors must have grown from such small foci originally.
Leslie J De Groot,MD
THERAPY OF THYROID CANCER WITH KNOW POSITIVE NECK NODES, ELEVATED TG,
AND NEGATIVE SCAN? 1 Nov 02
I am writing to seek your opinion on a patient
who has been treated and followed up by one of my colleagues and
recently I was involved in his management. A detailed medical
report is attached but briefly he is a 33-year-old man who had papillary
thyroid cancer of 4.5 cm size with lymph node mets. He underwent
total thyroidectomy and bilateral modified neck dissection in May 1999.
He was subsequently treated with 136 mci iodine-131 for local neck
uptake and unsuppressed Tg of 0.7 mcg/l. His follow up was marked
by slightly elevated unsuppressed Tg levels ( 2.7 and 3.5 mcg/l) but
negative diagnostic WBS and essentially negative US examinations.
In June 2002, his Tg rose to 1.4 mcg/l while he was on 0.2 mg L-thyroxine. In
October 2002, Tg was 29 mcg/l off treatment. Radioiodine
Whole body scan is negative but US showed 5 and 8 mm right cervical
lymph nodes and FNA from one of them was positive. PET scan
showed uptake in the lower neck but no other uptake. CT chest
showed no lung mets. The question basically is what would you
recommend at this stage? Thank you in advance for your help.
Ali Alzahrani, M.D.,King Faisal Specialist Hospital & Research
Center,MBC-46, P.O. BOX 3354, Riyadh 11211, Saudi Arabia.
RESPONSE-Your patient has residual tumor at least in neck
node(?s). Possibly the nodes would take up RAI and be treated to some
extent by a large RAI dose at this point. This approach is followed
by some physicians when the source of the TG is unknown. However I would
favor first removal of the known positive node (or more likely nodes) by
surgery. The stimulated TG of 29 indicates a significant amount of
functioning tumor, so the neck nodes may be only part of the
problem. If the TG remains signficantly elevated after node
resection, and no other source can be identified by neck MRI and US, and
his chest CAT is negative, RAI therapy may then be appropriate. You
may also want to do abdominal CAT and bone scan in your survey for mets.
Of course the value of treating such TG levels "blindly" with
large doses of RAI is still debated, but your patient is young and thus
aggressive therapy is reasonable.
Leslie J De Groot,MD
TRANSIENT HYPOTHYROIDISM, AND AN ELEVATED RAIU
Monday, September 16, 2002 8:54 PM
May I get your opinion on the following case:
22 year old woman with presents to her primary provider with
complaints of amenorrhea times 6 months. Additional concerns
include cold intolerance, dry skin, hair loss and an 18lb weight gain over
the past year.
In March of this year TSH 2.54.. On 8/14/02 TSH 52.43, Free T4
0.62 (nl .68-1.76).
On 9/9/02 TSH 30.61, free T4 0.69, T3 118, TPO ab 972.
Primary provider orders thyroid uptake and scan which are completed on
9/12/02, prior to her evaluation in the endocrine clinic 9/16/02. The scan
shows a diffuse goiter. The 6 hour uptake is 32%.
In endocrine clinic the above history is obtained.
examination is notable only for a diffuse goiter about 2 times normal
size, which is non-tender.
Can we explain this mixture of findings based on an acquired defect >
of iodide organification secondary to TPO ab inhibition of thyroid
peroxidase? If not, what might be the cause of the high uptake at
the same time as the high TSH and low free T4 levels. Would you not
just go ahead and put her on L-T4 replacement therapy?
Thank-you so much for your assistance,
Karen Kartun, M.D., Kaiser Permanente
Division of Endocrinology,
9985 Sierra Avenue’> Fontana, CA 92335
BY DR ANTHONY WEETMAN
This patient clearly has autoimmune thyroid disease as shown by the
positive TPO antibodies. There has been a very rapid change in thyroid
function, from a normal TSH to a value of 50 in 6 months and then a
rapid fall, with only barely reduced T4 levels at the peak of TSH and a
normal T4 on the last value we are given.
Although TPO antibodies may inhibit TPO enzyme activity in vitro, these
data are controversial and there is no in vivo evidence to support this
type of action. For instance TPO antibodies are transferred across the
placenta yet the babies of such mothers with high TPO antibodies have
normal thyroid function.
Goitrous autoimmune hypothyroidism with an elevated TSH is a known cause
of increased radioiodine uptake (1). I suspect that this is the
diagnosis here and the pattern of thyroid function fits with a
recovering phase of silent thyoiditis in such a gland. Whether the
increased uptake is solely mediated by the elevated TSH or is due to
coincidental thyroid stimulating antibodies, which occur in some
patients, could only be assessed by measuring these antibodies but I do
not think this test is strictly necessary. I would simply ensure that
the patient is not taking iodine supplements intermittently, and monitor
thyroid function regularly, say every 3- 4 weeks; the latest T4 level is
normal and therefore there is no need to start thyroxine until the
pattern of illness shows this is needed. If normal thyroid function
resumes, regular followup will be required.
1. McDougall IR, Cavalieri RR. In vivo radionuclide tests and imaging.
In Werner and Ingbar's The Thyroid. 8th edition Eds Braverman LE,
Utiger RD, Lippincott, Philadelphia pp355-375
another contributor note that the last values fit with subclinical
hypothyroidism, and some practitioners - (including this one) would feel
safer starting replacement T4 at this time.
L De Groot,MD
IS THIS GRAVES’
DISEASE? 1 Oct 02
I recently saw a 25 year old male law student with hyperthyroidism.
He came with a diagnosis of Graves disease made about 3 years previously
(solely on clinical grounds as far as I can tell). He was treated
with PTU with control of symptoms for about 1 and 1/2 year after which he
stopped the drug. His hyperthyroidism returned over the course of
several weeks to a few months. When he presented 2 months ago, he
had been of the PTU about a year and was symptomatically hyperthyroid. The
hyperthyroidism was interfering with his law studies. He was
tachycardic, diaphoretic and tremulous on exam. His thyroid was
twice enlarged and diffusely so. No nodules were appreciated,
although on serial exams there does appear to be some inhomogeneity in the
texture of the gland. His thyroid function tests showed and
undetectable TSH <0.01 and and elevated FT4 of 3.2 and a elevated Total
T3 of 250. I discussed options with him regarding treatment and he
decided to consider I131 but wanted to restart PTU for now. I convinced
him to obtain a I123 study to calculate a dose for I131 and confirm the
Graves diagnosis. He delayed and only did the I123 after 2 to 3
weeks of PTU therapy and improvement in his symptoms. I took him off
the PTU for 2 weeks (after the 3 week therapy) and obtained the I123 scan.
His 6 and 24 hour uptakes were at the upper limits of normal. 33% or
so at 24 hours. The scan showed heterogeneous uptake.
Antimicrosomal (antiTPO) antibodies were strongly positive but a TSI assay
I thus have two questions-
1. Diagnoisis - is this patient's diagnosis atypical Graves, a
variant of toxic multinodular goiter, Graves with in a multinodular
goiter, transition from Hashimoto's to Graves?
2. What would be the best course of therapy? Would I-131 be
Thanks very much for any insight.
Coleman Gross, MD
Specialty Clinics, University Health Service,Tang Center,2222 Bancroft
Way, Berkeley, CA 94720
by Leslie J De Groot,MD
The clinical picture is certainly most compatible with Graves, in view of
the rapid relapse, youth, male sex, non-lumpy gland, and + TPO-Ab. I
suppose a toxic multinodular goiter might present this way, but it would
be unusual. A non-homogenous scan is not rare, probably because of
the variable extent of coexistent thyroiditis in various parts of the
gland. Obviously an US might be informative, but I do not think you
really need it if you can feel the gland and do not feel lumps. Since he
relapsed from one course of ATD, he probably would do so again. Thus
I believe most thyroidologists would offer RAI as the next therapy, and I
do not see any contraindication from what you report. If you have a
capable surgeon available, surgery is also reasonable to consider,
especially if he has significant ophthalmopathy.
QUESTION- WHEN IS A PENTAGASTRIN TEST ADVISED IN FOLLOWING MTC/
I would like to see more information about the use of pentagastrin-stimulated
CT secretion as a test to determine whether thyroidectomy is to be
recommended in persons with the C609Y (or other relevant location) mutant
RET proto-oncogene on chromosome 10. It appears that some physicians
recommend thyroidectomy in such a case without ordering the test. The only
place where I see it briefly mentioned in the ThyroidManager web site is
<http://www.thyroidmanager.org/Chapter18/18-medullar.htm> Yours, L.
David Roper: email@example.com
RESPONSE from Dr Furio Pacini-Dear
Dr. Roper- I received your question about the utility
of pentagastrin test in patients with C609Y ret mutation. This mutation
has been reported in association with familial isolated medullary thyroid
cancer (FMTC). As is the case with mutations in other codons associated
with FMTC, the consensus agreement proposed in several congress of the MEN
2 study group is that pentagastrin test it is always advise in gene
carriers of FMTC to ascertain whether some minimal disease is already
present. If a significant response of calcitonin to pentagastrin
stimulation is present (or if some other clinical features are suspicious)
thyroidectomy is advise. If not, thyroidectomy may be delayed, although
some authors prefer to propose surgery even if pentagastrin test is
negative. I hope that this clarification may answer your question.
Sincerely F. Pacini MD
HOW TO TREAT SUB-CLINICAL HYPOTHYROIDISM?
One of my patients is a lady
aged 48 years. She has most signs and symptoms that correlate with
hypothyroidism. Her TSH is 9.7 mlu/L ( range 0.27-4.2), T4 is 13 pmol/L
(range 12-22), T3 is 4.7 pmol/L (range 2.8-7.1) . There is no relevant
history. She is having menorrhagia (severe) , shortness of breath, iron
deficiency anemia, obesity, lemon yellow color, flushing of checks, BP=
170/90, diabetic since one year (type 2) , had rough skin, complain always
of somnolence , general weakness and sweating. Please send for me your
opinion and plan for management and should we consider it as a case of
overt hypothyroidism or a subclinical one.
Thanks for your cooperation.
Dr Attallah, your patient has still a T4 and T3 within the normal range
and should therefore be classified as subclinically hypothyroid. It is
difficult to assess if her complaints are due to hypothyroidism and/or to
her diabetes in combination with obesity. On the other hand the level of
TSH and free T4 are at the border of overt hypothyroidism and my advise to
you is to determine her thyroid auto-antibodies and to treat her with
thyroid hormone such that her final TSH finally drops between 0.27 and
maximally 2.0 mU/l. If antibodies are present in the serum, than it is
almost certain that she will eventually develop full blown hypothyroidism
and in that case treatment should be continued irrespective of any
immediate effect. If antibodies are absent and T4 substitution has no
effect discontinuation of T4 could be considered but the patient should be
frequently seen in follow up.
Georg Hennemann, MD, PhD, FRCP, FRCP(E)
E mail: firstname.lastname@example.org
How to manage existing hypothyroidism perioperatively in a patient NPO ?
I was called to evaluate a 82 year old female with cholecystitis who had
hypothyroidism and has been taking levothyroxine 125 mcg/day. Her last TFT was
fT4- 1.3; TSH - 6.1 three days ago. Patient is NPO. Suction tube is in place. It is on
constant suction. There is a plan for surgery in 5-7 days. Should be levothyroxine be given IV or
withheld for a short period of time. Thank you for your service. I always read all your
Q&A section. It is very useful. Feel free to publish my question if you find it interesting enough for
physicians. Sincerely yours, Dmitri Kirpichnikov email@example.com
Kirpichnikov, MD, 9711 Third Ave, Brooklyn, NY 11209
RESPONSE-No problem to withhold it for a few days. Regards, Georg
QUESTION- HOW LONG TO WAIT AFTER OPERATION BEFORE RAI ABLATION?
Dear experts -In the literature it is always suggested that the radio iodine
abalation is administered approx 4-6 weeks post operatively after total /near total thyroidectomy for ca. One of the reasonS is for stimulation of
TSH so it is at least above 30 mIU/L, but if this level of TSH is reached before this period( by end of first week? ) can RAI be
administered sooner ? Thanks
Hamda Saleh, Registrar,The Children's Hospital at Westmead,NSW,Australia
612-98452905 Nasir Kahlon <firstname.lastname@example.org>
ANSWER-I am not aware of any reason that one needs to wait longer than the interval required to raise the TSH, or of a study on the question. Note that the TSH may go up slowly or never reach 30 if a large amount of thyroid is left in
place. The prior approach involved allowing patients to recover from the operation, and then preparing for
ablation. Probably either way is acceptable.
Leslie J De Groot,MD
QUESTION - DO WE REALLY NEED TO DO BOTH fT4 AND TSH IN
Sincere admiration for your great website. Regarding evaluation of
thyroxine replacement therapy, it is always suggested to evaluate TSH
and free T4. However except in the situation of pregnancy (where only
depending on TSH could result in a retarded action), I don' t see much reason to
determine both values. Is it wrong to check only TSH ?
Dr. Henri Maex, Antwerp, Belgium Email- Henri Maex <email@example.com>
QUESTION- HOW TO MANAGE FETAL HYPOTHYROIDISM AND GOITER
Dear expert: Patient is a 29 yr old lady - 26 weeks intauterine
pregnant. She has had an earlier miscarriage at 6 wks gestation - cause
unknown. Not a consanguinous marriage. Routine ultrasound at 26 weeks
revealed a fetal goiter - 3.5 x 2.5x 2.5 cms. Weeks of gestation by
ultrasound corresponds to gestational age by LMP. Pregnancy is otherwise
normal without any other complications. There are not from endemic areas
for iodine deff.Mother's thyroid function tests are normal - TSH and Free
T4 . Her Antithyroid peroxidase antibodies are negative. Cord blood TSH is
> 100, Free T4 - 2.5 (4.2 - 6.2),Anti TPO is negative. IV levothyroxine
is avialable with difficulty and very expensive - Rs 8000/ per 100 Ucg.
These are mothers and my
1) Will the baby's IQ be completely normal with treatment
with intra-amniotic LT4?
2) What are the chances of a similar problem in subsequent pregnancies -
as she is considering an MTP if the
chance of normalization OF IQ
of the child is not
Other queries are:
1) What would be the dose of IV
levothyroxine -intra-amniotic - would a loading dose be required?
2) How soon would the goiter shrink and will it shrink completely???
3) Would oral LT4 in high doses be of any use at all, since cost is a
4) Would u recommend an MTP to this patient?
We would appreciate a prompt response so that a decision can be made soon.
Radha Reddy MD (Endocrinology and Diabetes, USA), Consultant
Mallya Hospital, Bangalore, India
June 06, 2002 8:58 PM
BY DR ROSALIND BROWN
Dear Dr. Reddy: I
find your case most unique and perplexing since the baby appears to have quite
severe fetal hypothyroidism despite the apparent absence of either thyroid
disease or medication in the mother.
Therefore, one would need to hypothesize
both fetal thyroid disease (presumably due to an abnormality of thyroid
hormonogesis) as well as the absence of adequate maternal thyroid hormone
to at least partially compensate for the severe fetal hypothyroidism. I
would therefore think that before embarking on intraamniotic T4, it is
most important to be absolutely sure that the mother is not taking
something (e.g., a homeopathic remedy, or iodine-containing medicine for
asthma, etc.) that might preferentially affect the baby's thyroid
answer to your questions:
1)Although there are no guarantees in medicine, the baby's IQ should be
normal with intramniotic T4. By analogy, babies with no thyroid gland at
all have normal cognitive development even with POSTnatal treatment as
long as treatment is sufficiently early and adequate.
I personally have never advocated
intraamniotic T4 since usually my preference would be to reduce the dosage
of antithyroid medication in the mother (in cases of maternal Graves'
disease). I would, however, in your case due to the severity of the
hypothyroidism, not to mention the presence of fetal goiter which, if
sufficiently large, can cause respiratory obstruction and distress.
2) Most cases of thyroid dyshormonogenesis are autosomal recessive and
therefore carry with them a 1/4 chance of recurrence in each pregnancy. It
is now possible to determine the molecular etiology of many of these cases
although this is usually only done in research laboratories and clearly,
if the molecular etiology were known one could even do fetal diagnosis.
3) The doses of L-T4 that have been used in the literature are 250-500
micrograms, given every 1-2 weeks as necessary. Improvement in the TFT's
and shrinkage of the goiter are observed within a few weeks. (cf: Perelman
AH et al, JCEM 71:618, 1989;Davidson KM et al, NEJM 324:543,
1991;Vicens-Calvet E et al, J Pediatr 133: 147,1998).
4) Yes (see (1)
S. Brown, MD,Professor of Pediatrics,
University of Massachusetts Medical School,
Director, Division of Pediatric Endocrinology/Diabetes
UMass Memorial Health Care <Rosalind.Brown@umassmed.edu>
QUESTION- PATIENT SEEKS COUNSELING ABOUT THE POSSIBILITY OF FUTURE THYROID
In brief he is a 40 year old male who presented in his early 30s with
hypothyroid symptoms and a modest goiter of several month's duration. A
family history of transient hypothyroidism, possibly in the setting of
pregnancy, was reported. An elevated TSH and low total T4 were found and
corrected with Synthroid. His symptoms completely resolved. No other
testing was performed at that time.
In the intervening years he experienced increasing sinus and rhinitis
symptoms and he failed medication therapy. He underwnet endoscopic
surgery, which alleviated his sinus symptoms but his rhinitis persisted.
Annual TSH testing was normal on a steady dose of Synthroid.
In mid-2001 he suffered a severe, persistent URI with intermittent
low-grade temperatures for several months (another family member had a
similar URI course). After six weeks of URI symptoms and severe rhinitis
he began experiencing what in retrospect appear to be hyperthyroid
symptoms (sweating and tachycardia). TSH was in the mid-normal range in
mid-2001 but fell to just beneath the normal range by fall 2001.
Unfortunately free T4 was not measured. Synthroid was held and beta
blockade introduced until TSH returned to normal. Steroid was not
administered because of ongoing URI symptoms.
His low-grade fever from the previous illness had resolved in the interim,
but when sharing new household viral illnesses in late 2001, intermittent
sweating and hyperdynamic symptoms recurred for brief durations when
acutely ill. By spring 2002 his hyperdynamic symptoms slowly abated and
his TSH rose (and hypothyroid symptoms recurred). As of mid 2002 he is on
his baseline dose of Synthroid with normal TSH, normal free T4, and normal
Immunological testing performed before his TSH was found to have fallen
was unremarkable except for a modest IgE spike. His ESR was never
elevated. Viral testing was negative. A bone marrow (performed because of
the combination of low-grade fevers and sweating) had a gross appearance
remininscent of pernicious anemia but testing was unremarkable (felt to be
"reactive", consistent with either an autoimmune state or viral
A thyroid ultrasound was consistent with Hashimoto's thyroiditis of
uncertain duration. Thyroid antibodies were moderately elevated, also
consistent with thyroiditis of unclear duration. Of note is that a PET
scan, done as part of the work-up prior to frank TSH changes, showed
intense thyroid uptake.
He now returns concerned about the possibility of future recurrence. At
present he is euthyroid but has ongoing rhinitis symptoms. Other findings
C. L. Etheridge, MD firstname.lastname@example.org
ANSWER BY LESLIE J DE GROOT, MD
I believe you describe one of the more unusual, but not unique,
presentations of autoimmune thyroid disease. Probably this is best
classified as "Hashimoto'sThyrodiitis". The course, with periods
of hyperthyroidism and hypothyroidism, is occasionally seen. Presumably
this is related to changes in the types of antibodies being produced
(stimulatory vs inhibitory) or the intensity of the T cell response. The
relation to sinusitis (or another infection) is probably real, and has
been reported by Amino and co-workers, along with the elevation of
IgE. One presumes that the release of cytokines into the circulation
(IL-1, IL-2, Il-L-6, IFN gamma, TNF alpha) is the actual cause of the
changes in the thyroid inflammatory process. Sometimes the process seems
to have a mixture with SAT, with thyroid pain and tenderness, but in your
case the low sed rate rules out that process as the primary
diagnosis. I think there is a strong likelihood of recurrence. While
use of steroids might control the process temporarily, the only
"solution" I know of, if the problem is severe enough to merit
such , would be to remove the thyroid by either RAI or surgery, and I
would favor the latter if a good surgeon is available.
Leslie J De Groot, Univ of Chicago, Chicago, IL 60637 email@example.com
QUESTION- "HASHIMOTO'S ENCEPHALITIS"
Dear Thyroid experts :I had a patient who was admitted to hospital with confusion. she is 39 yo with known
Hashimotos found last month to present with tonic-clonic seizure.
Not doing well for one month and problems with word finding. ct at outlying hospital reported as cerebral edema.
EEG revealed bifrontal rhythms and polymorphic slowing. Had a ventriculostomy placed due to CSF pressure of 20. Pt discharged and then represented with confusion ...Further investigations showed questionable cerebritis around ventriculostomy site on MRI . Other w/u at outside hospital neg HSV/PCR, transthoracic echo neg, CT angiogram positive for
PE with positive anticardiolipin antibody. Pt then anticoagulated prior to transfer to our institution---
Found to have elevated microsomal ab 1:6400, and anti TPO 2517. Patient was
seen by rheumatologist with negative workup at our institution (neg for
ANA, anti DNA , anti RNA, SSA, SSB, SCL70 and chromatin antibodies negative, c3 208 ).
Underwent plasmapheresis and steroids. She was then place on prednisone 100mg /d.
No other residual neurological problems. No other explanation by rheum who felt the original antibodies for anticardiolipn was negligible (am trying to get records).
I had seen her one year ago with a goiter about 120g and placed her on thyroid hormone for
biopsy positive autoimmune thyroid Hashimotos.
Other complicating history--with PE dx on coumadin, not optimal surgical candidate at this time.
Is there some information /references on Hashimoto's encephalopathy/cerebritis as that is the suspected diagnosis by the rheumatologist. . If this is true -optimal treatment?
Ablation with I-131 vs surgical resection of goiter?....Should I be worried about thyroid lymphoma ?
Re bx ? Re-ultrasound thyroid for size pending.
Appreciate any input or recommendations for further history or
anne marie lee
2220 riverside ave s
mpls, mn 55454
univ of mn clinical asst professor
RESPONSE BY LESLIE J DE GROOT,MD-- Surely your case fits into the
category of "Hashimoto's encephalitis". By now there have
been more than 50 similar patients reported.-(Neurology 1991:41:223-233,
Neurol 1996;243:585-593, Neurology 1997;49:623-626, Euro Neurol
1999;41:79-84, and many others on Medline). The manifestations are
typically confusion, obtundation, dementia, seizures, sometimes psychosis,
movement disorders, stroke-like episodes with abnormal EEG, variable minor
abnormalities on CAT or MRI, sometimes elevated CSF protein, and typical
findings of Hashimoto's with high antibodies. Usually the patients respond
to prednisone, and some have been given other therapies including IV IgG
and cyclophosphamide. Some do not respond totally. I am not aware that
removal of the thyroid by surgery and 131-I has been reported or
attempted, although it obviously is an interesting idea. If the patient
fails to respond to immuno-suppressive therapy , one could make a case for
total removal of thyroid antigens. However I must immediately point
out that there is absolutely no published support or experience with this
approach, so far as I know.
There is as yet no consensus
that this is "due to " Hashimoto's thyroiditis and its
autoimmunity. Some observers believe this is the case, and
others contend that it is simply the combination of some yet undiagnosed
unusual encephalitis, and a fairly common thyroid disease. My bias
is that it will be found to be tied in some way to autoimmunity to CNS
antigens that somehow overlap with antigens in the thyroid.
Leslie J De Groot, MD Univ of Chicago/Endocrinology
BY DR. NOBUYUKI AMINO - Your case is compatible with so called
Hashimoto’s encephalopathy or encephalitis, although the existence of
such a specific disease is not completely established. As you know
Hashimoto’s thyroiditis is very common. Around
10 % of adult women in the general population have positive anti-thyroid
microsomal antibodies. Thus I speculate that an autoimmune encephalitis is
coincidentally associated with Hashimoto’s thyroiditis. It is well known
that Hashimoto’s thyroiditis frequently aggravates during the postpartum
period, but development of associated encephalopathy has not been
reported. Therefore I believe that encephalopathy in your patient might
occurred independently from Hashimoto’s thyroiditis. Therefore total
thyroidectomy may not release the patient’s symptoms. We need more
definitive evidence that encephalopathy is really causatively associated
with autoimmune thyroid disease. In your case, the patient is suffered
from PE, and has positive anticardiolipin antibodies. It is strongly
suggested that encephalopathy might be related to a vascular problem
induced by an autoimmune mechanism, such as lupus anticoagulant and/or
other antibodies to various coagulation factors. As reported in other
patients, steroid therapy would be preferable, if patient relapses.
QUESTION- PRIMARY VS SECONDARY
HYPOTHYROIDISM ?- AND
One of my patient is a 54 y.o., poor, medically uninsured female suffering
evidently from hypothyroidism: since 2 years, she has become progressively
fatter, weaker, has menorrhagia, hoarseness of her voice, decrease
hearing, and feels depressed. She also complains of dry skin and water
retention. Her condition has been attributed to premenopause and
depression which are under no treatment because she does not tolerate
HRT or antidepressants.On examination, I noticed edema of the face and
extremities, bradycardia at 50-60 bpm, and a lag in relaxation of knee
jerks. The cranial nerves were intact, the blood pressure was 120/80, the
visual fields normal by confrontation, the fundi normal, and the untanned
areas of her skin had no discoloration.To minimize her lab cost, I first
ordered a TSH($28) only: it came back normal at 1.2 !Subsequent FT4 came
low at 7.
Since there is no evidence of adrenal hypofunction on
physical examination, can I start Levothyroxine now, and save the patient
a costly serum ACTH determination ?
What can I do about the possibility of a pituitary tumor in this patient
who cannot afford a $2500 MRI or CT scan ? Would a simple skull x-ray or
tomogram of the sella turcica sufficient ? Should I wait for the possible
adenoma to shrink under T4 replacement before imaging studies ?
I would appreciate your "off the book" opinion and
recommendations based on your experience with central hypothyroidism
taking into consideration the limited paying capacity of this
Thank you very much for your work on this website.
Aloha and Mahalo !
Dr. Michel Soucy, P.O.Box 63,Hawi, Hawaii 96755; 808-889-6223 firstname.lastname@example.org
ANSWER BY DR. WILMAR WIERSINGA
is an interesting case because the clinical examination clearly
demonstrates hypothyroid signs and symptoms, but the serum TSH comes back
normal! Still, serum FT4 is decreased, and the straightforward diagnosis
is then central hypothyroidism. The question is if this patient can safely
be started on thyroxine without knowing if central hypothyroidism is
absent. For, starting thyroxine in a patient with hypocortisolism may
provoke an Addison's crisis. Although physical examination didn't give a
clue on the existence of cortisol deficiency, this by no means rules out
hypoadrenalism. Dr. Soucy is reluctant to order more tests because the
finances of the patient do not allow this. Certainly the ACTH assay would
be a bad idea, because ACTH in central hypoadrenalism is not elevated and
the ACTH assay cannot reliably discriminate between normal and subnormal
values. Also a single plasma
cortisol test will not answer the question because a random cortisol may
be normal despite the presence of hypoadrenalism. A dynamic test (ACTH
stim test, insulin tolerance test, or metyrapone test) would be indicated
to diagnose central hypoadrenalism, but this might be too expensive for
the patient as well, and can be dangerous if not carefully supervised.
is it really central hypothyroidism? This entity is not very prevalent. In
this age group (54 years) the most likely cause is a pituitary adenoma -
the mass effect reduces pituitary hormone secretion. However, in most
cases of pituitary adenomas the first hormones which fail are GH and the
gonadotropins; TSH and ACTH follow much later. Consequently, isolated TSH
deficiency is rare, and in this particular patient should be associated
with loss of gonadotropin secretion as well. But, we are informed that the
patient is not amenorrheic but has menorrhagia which speaks against
So, is the
TSH value of 1.2 mU/l a valid one? Is the assumption that there is no
interference in the TSH assay by heterophilic antobodies? Could there have
been an error in the lab, or switch of samples? After all, the pre-test
likelihood of primary hypothyroidism in this lady is pretty high, much
higher than that of central hypothyroidism. I would therefore put my money
on a repeat TSH-test, or on a TPO-antibody test. If one of these tests
results in an elevated value that is clear evidence of primary thyroid
course, primary autoimmune hypothyroidism is associated with primary
autoimmune adrenal failure, which if unrecognized puts the patient again
at risk for developing Addison's crisis if only treated with thyroxine.
But the co-existence of these two disorders is less frequent than that of
ACTH-deficiency in adults. I think the patient needs thyroxine treatment.
If money is lacking to do some
supplementary tests, I would start her on thyroxine alone, under the
specific instruction to call or see me directly when in the coming weeks
she feels not better but worse, becomes nauseated or dizzy etc. This must
be a feasible management plan: after all, Hawaii is not that big an
island! ( ED-At least an 8 AM cortisol, FSH, and lateral skull x-ray could
be checked despite the financial constraints, and further evaluation done
depending on these results. Correct diagnosis is very important here
QUESTION-DOES THIS PERSON
HAVE “THYROID HORMONE
Case submitted by Dr Karen Kartun.
History: This 54-year-old woman is referred for a thyroid evaluation. She
was originally diagnosed as hyperthyroid about 20 years ago when she
presented with complaints of irritability, feeling "hyper" and
general malaise. That had been present for many years before her
presentation to this physician. She was treated with radioactive iodine at
that time at another facility. Those records are not available. She was
subsequently given L-T4 replacement therapy but has never been able to get
her levels balanced out since that time. She has persistently had an
elevated TSH level with an elevated free T4 level on varying doses of
thyroid hormone. She is currently treated with Levothroid 212 mcg daily.
She has been consistent in taking her medication everyday. Currently she
has some complaints of heat intolerance. She has irritable bowel syndrome
and some complaints of hair loss. Weight loss has been difficult for her
and she maintains the weight in the mid 170s. She has had some increased
blotchiness of the skin recently. She has no complaints of edema, muscle
cramps, nervousness, palpitations, or tremor. She is troubled by
depression which is treated with Effexor. Her mother had a goiter which
was resected. She does not know of any other family with thyroid
Past Medical/Surgical History: (1) Thyroid disease as above. (2)
Depression. (3) Irritable bowel syndrome. (4) Status post hysterectomy.
(5) History of hand and foot surgeries. (6) Hypertension.
Medications: (1) Levothroid 212 mcg q.d. (2) Premarin 0.9 mg q.d., (3)
Effexor 150 mg b.i.d. (4) Atenolol 25 mg q.d.
Family History: Mother died at 62 with history of thyroid and heart
disease. Father died at 68 with a CVA in his history.
Siblings - she has a brother who committed suicide and a sister who died
of a brain tumor. She has 4 children, one who has had cerebral palsy, the
others are healthy.
Social History: She does not smoke cigarettes, drinks alcohol
Review of systems: negative except as above
Examination: Blood Pressure: 118/66. Height: 5 feet 3.5 inches. Weight:
176 pounds. Pulse: 59. Temperature: 96.4°. She was alert and oriented x 3
and well appearing. HEENT: Extraocular movements were intact. Pupils are
equal and round. There was no lid lag, there was no proptosis. Visual
fields were intact to confrontation. Neck: Supple. No lymph nodes are
palpated. Thyroid did not show a goiter. Lungs: Clear to auscultation.
Cardiac Exam: Normal S1/S2. Abdomen: Soft and nontender. Back: Negative
for CVA or spinal tenderness. Extremities: Negative for edema. Neuro Exam:
Shows 2+ deep tendon reflexes and a tremor was noted.
Laboratory studies were reviewed. In 11/99 her TSH was 18.23(0.35-6) with
a free T4 of 1.79(0.68-1.76), 7/9/01 her TSH was 15.13, free T4 2.09,
8/14/01 TSH 10.62 (0.35-6),
free T4 1.87(0.68-1.76), total T3 210 (58-184)with an FSH level of 29.9,
LH of 24.3, prolactin 65.8 (1.6- 27.1), and am cortisol 16.8,
8/20/01 TSH 4.98, free T4 2.55, T3 211. All of those laboratory studies
were done on doses of thyroid hormone replacement greater than 200 mcg
Dr Kartun,s evaluation: This is a very strange story and group of
laboratory results. It would be extremely helpful to see the original
thyroid function tests and Nuclear Medicine scan report from the time of
her initial diagnosis 20 years ago even though her symptoms date back even
further than that. There are several possible explanations for her levels;
(a) patients who do not take their Levothroid regularly as prescribed can
get an elevated TSH level. Sometimes if they take a large number of
tablets right before their laboratory tests are done in hopes of
normalizing their levels you can see the high free T4 level with an
elevated TSH, (b) patients with thyroid hormone resistance can have
similar levels. This is a genetic disease which is inherited as an
autosomal dominant trait. Therefore, we would expect other family members
to have been similarly affected. We do not have a definite history of
other affected family members though Ms. James suspects that her daughter
may have similar problems, or (c) patients' with TSH secreting pituitary
adenomas could have similar laboratory values. It seems as if it would be
unlikely that a patient with a TSH secreting adenoma would not be made
even more hyperthyroid than baseline levels by the addition of the very
high doses of L-T4 she is already receiving. Although this has been going
on for 20 years it seems hard to imagine that a TSH secreting adenoma
could be missed for that many years. However, in reviewing the literature,
there are reports that note the length of time from the onset of symptoms
to the time of diagnosis varies from 1-27 years. Many of these patients
have received I-131 therapy in the past. Bonnie does not have a goiter and
she does not have visual field defects that are obvious. Her FSH and LH
are appropriately elevated for a menopausal woman. Her prolactin is
moderately elevated and TSH secreting adenomas can co-secrete prolactin or
possibly a pituitary tumor can cause stalk compression leading to an
elevated prolactin level. Hypothyroidism can also cause prolactin levels
to go up because TRH is a prolactin secretagogue. Her cortisol levels are
Assuming that the patient is honest and her compliance with her therapy
has been good we need to differentiate between the latter 2 possibilities.
An SHBG is elevated in patients with adenomas and normal in those with
thyroid hormone resistance. An alpha subunit is elevated in adenomas and
normal in resistance to thyroid hormone. If this were an adenoma the
patient theoretically would not require L-T4 therapy and if we decrease it
or stop it she should still have an elevated free T4 level unless her
prior radioactive iodine therapy did knock out her endogenous thyroid
function and her TSH is not suppressible by the overdosage of L-T4 therapy
she is currently receiving. We do need to tease these things out.
The plan is as follows: (1) Decrease L-T4 to 150 mcg daily and repeat
thyroid function tests in 6 weeks. (2) Will check a TSH, a free T4, a
total T3, a prolactin, an IGF-1 level today and an SHBG and an alpha
subunit. (3) It is okay to go ahead with the pituitary MRI scheduled for
10/23 but no therapy should be instituted prior to obtaining the results
of the above laboratory studies.
Additional results since the date of the initial consultation--
10/12/01 SHBG 49.1 (18-114) , PROLACTIN 50.0 (1.6-27.1) , T3 165 (58-184)
,FREE T4 1.80 (0.68-1.76) ,TSH 10.55 (0.3506)
IGF-1 138 (90-360) ,ALPHA SUB UNIT 0.2
10/23/01 MRI-vague hypodensity (<1cm) in the right inferolateral
pituitary which persists with contrast enhancement.
Stalk and chiasm normal. There was mild sloping of the sellar floor.
On 150mcg L-T4 QD: 11/28/01 T3 143 (58-184) ,FREE T4 1.29 (0.68-1.76) ,TSH
just got back another interesting piece of information.
I had the case patient's daughter tested.
Her TSH is 1.92 (0.35-6), her free T4 is 2.08 (0.68-1.76) and her
total T3 is 236 (58-184). She
is not on any thyroid hormone and has never had any form of thyroid
treatment. This looks to me
like thyroid hormone resistance in this family.
Would you agree? If so how do I determine the appropriate
of free T4/TSH at which to keep the case patient?
Department of Medicine , Division of Endocrinology, Kaiser
Permanente ,9985 Sierra Avenue ,Fontana, CA 92335 ,(909)427-3334
BY DR SAMUEL REFETOFF – (12/20/01)
the follow-up on this case, it is obvious that Dr. Kartun does not need
the help of "an expert". Short
of demonstrating a mutation in the thyroid hormone receptor
(TR) beta gene, the diagnosis of resistance to thyroid hormone (RTH)
is almost certain. I would
like, however, to take this opportunity to make a few comment that may be
helpful to practicing physicians.
Because RTH is inherited, a simple and direct approach to the
diagnosis is to test family members.
This always proves to be cost effective, considering the additional
tests, such as MRI, often used to rule out alternative diagnosis, are
quite pricey. Testing family
members is particularly helpful when the study of the key case is
complicated by prior ablative therapy and the requirement of hormone
replacement. The fact that
RTH is inherited as a dominant trait
reduces the number of individuals that need to be examined, since,
one of the parents must be affected and 50% of siblings and progeny would
manifest the phenotype (high serum free T4 and T3 levels with normal TSH).
Having said that study of family members is the cornerstone in the
diagnosis, it is important to note that 10% of TR beta gene mutation occur
de novo. Thus, the key case
may be the first family member carrying the TR beta gene mutation.
Furthermore, in another 10% of individuals with RTH, the phenotype
is not caused by mutations in the TR beta gene.
In such instances, additional tests are required to establish the
A solid clinical proof that elevated serum free T4 and free T3
levels with non-suppressed TSH is due to RTH is the measurement of
responses to exogenous thyroid hormone given in incremental doses.
A relatively simple and established protocol is the administration
of graded doses of T3 (50, 100, and 200 micrograms/day) each given in two
divided doses for three days. The
baseline and following each dose central and peripheral parameters of
thyroid hormone action are measured and the changes compared to data
available from unaffected controls.
measurements of peripheral markers of thyroid hormone action, such as,
cholesterol, SHBG (measured in this case), ferritin, and creatine kinase
are of little value because of the broad normal range and unrelated
conditions that could affect their levels.
It is the change in their response to thyroid hormone
administration that is valuable for the diagnosis of RTH.
Finally, I would like to point out several findings in Dr. Kartun's
case that are of interest or important in the differential diagnosis as
well as additional simple tests that could have been of diagnostic value.
elevation of the serum free T4 concentration without TSH suppression is
not uncommon in individuals on L-T4 replacement.
However, in such instances, T3 remains in the normal range.
Similarly, patients with familial dysalbuminemic hyperthyroxinemia
(FDH) present with high T4 and even high free T4 levels (measured by
direct methods) and non-suppressed TSH.
With only rare exceptions, also these individuals have normal serum
T3 levels. Thus, in
considering the diagnosis of RTH, both free T4 and free T3 must be
RTH is most commonly mistaken as autoimmune thyroid disease (Graves'), the
absence of thyroid peroxidase, thyroglobulin and TSH receptor antibodies
could point towards the proper diagnosis.
goiter is absent and in patients who have not received prior ablative
therapy, measurement of the thyroidal radioiodide uptake could be of help.
It should be high in RTH but normal in thyroid hormone transport
defects, such as FDH.
prolactin is occasionally high in individuals with hypothyroidism.
This is also the case in individuals with RTH who are inadequately
replaced with thyroid hormone following ablative therapy.
normal alpha subunit and a normal response of TSH to TRH should be
sufficient as preliminary tests for TSH producing adenoma.
MRI of the pituitary which can be often abnormal due to
incidentalomas, should be reserved for those patients who have no living
relatives available for testing or when thyroid function tests in family
members have proven to be normal.
Recommendations regarding Dr. Kartun's case:
patient should be placed on sufficient amount of thyroid hormone to
maintain a normal TSH level. If
sinus tachycardia develops, Atenolol should be added to the treatment
remainder of the patient's children should be tested.
Those with abnormal thyroid function tests should be informed and
given letters explaining the cause. They
should be instructed to provide this letter to any physician who proposes
treatment for their thyroid tests abnormalities.
of the genetic defect is not mandatory.
However, in families in whom RTH is associated with growth
retardation, mental retardation or severe attention deficit disorder,
identification of the mutation could aid in providing future prenatal
THYROID HORMONE TREATMENT AND URIC ACID LEVEL
I have a patient with benign thyroid cyst
on suppressive therapy with 150 micrograms thyroxine . Her
thyroid function tests on this are :
Free T 4
6.8pmol/l range 3.3-7.2
S-TSH <0.01 0.2-0.4
Her uric acid is very low at
86micromols/l, range 140-390.
She also has a hip bursitis and shoulder
capsulitis, but ESR is normal, RF normal, and ANF normal. Her diet is
apparently normal. Using a MIRENA coil.
Is there any relation of the low uric acid
to the thyroid treatment
Clinic , PO Box 26777, Dubai , UAE
Answer by Dr Jim Stockigt
There is no description that I can find of
subnormal serum uric acid
associated with thyroid hormone excess. There is a useful section on
hypouricemia in the Harrison text, 14th Edn, p2165. Can you be sure
none of the medications used for the shoulder complaint have a uricosuric
One other comment. I wonder about the wisdom of using
therapy in a woman who may be at risk of osteoporosis, when the benefit of
such therapy in managing benign cysts is less than convincing.
thyrotoxicosis as a result of suppressive T4 certainly seems to
bone density ( see Wesche et al J Clin Endocrinol Metab 2001; 86:998-1005)
Regards, Jim Stockigt
THYROXINE REQUIREMENT DURING PREGNANCY
Friday, October 26, 2001 7:14 AM
One of my patients underwent total thyroidectomy because of failure of
drug treatment of Graves disease. One month postoperative she was
pregnant. Under 150 mcg T4 the TSH was 3.6 mU/L in the first trimester.
After 2 months it rose to 26 mU/L (under 170 mcg/d) and it was necessary
to give more T4: The TSH
normalised at the 6 month of pregnancy under 250 mcg/d (TSH 4.2 , fT4 18.6
pmol/l, fT3 3.5 pmol/l).
Today, around term, she
needs 5.8 mcg/kg effectve weight/d, or 7 mcg/kg prepartum weight/d) in
order to achieve a TSH of 1.4 I have no doubt about compliance (the
pharmacy confirms the correct amount of tablets). Normal weight, no
symptoms, fetal growth normal. (P.S.-Prepartum weight 50 Kg and during
pregnancy 57Kg).Is is an extreme form of physiological THR in
Many thanks for your answer.
Dr. Fabio Cattaneo, Lugano, Switzerland
ANSWER Wednesday, October 31, 2001 3:32 AM.It is
estimated that in almost all patients with thyroid deficiency (previously
having received radioiodine, or operated, or with autoimmune thyroid
disorders), the replacement dosage of l-T4 needs to be increased during
pregnancy. The guidelines to carry out this dosage increment are as
follows :1) it has to be done relatively rapidly during early gestation,
and certainly within the first trimester;2) the dosage increment needs to
be closely monitored during gestation, in order to avoid a rise in serum
TSH. In our experience, changes in l-T4 dosages occurred until
mid-gestation (5-6 months), and rarely in the last trimester (a
platteau is reached at this stage); 3) percentage-wise, the dosage
increment is approximately 30-60 % above baseline (preconception) daily
doses. However, this is an average, but does not tell us anything about
individual cases. Individually, l-T4 doses may have to be doubled (and
even higher); in our own experience, one compliant patient required above
300 mcg/d during pregnancy; 4) the final dosage increment depends upon
several factors that are difficult to predict:
- The functional reserve of the thyroidal
machinery : see the paper by Mike Kaplan, comparing pregnant patients with Hashimoto
(requiring a lesser increase) and thyroid ablation for cancer, etc
(requiring proportionally more);
- The rise in TSH (when it has occurred,
like in your case) is an additional difficulty, because then one often
runs "behind" the actual events taking place and it is sometimes
difficult to bring the TSH back to normal before the end of gestation (it
seems that you succeeded);
- Iodine deprivation : because of
increased needs for iodine during pregnancy, and its reduced availability in the pregnant
state, this may constitute an additional factor to complicate matters.
Obviously, this factor will only play a role when the iodine nutritional
status is limited, restricted, or deficient. Also, iodine deficiency will
obviously play no role (as in your patient) when a total thyroidectomy has
been performed previously;
- Thyroxine absorption by the digestive
tract : this has not been investigated so far, but we believe that some pregnant
women may have "malabsorption" of thyroxine;
- Changes in weight. I hope to have brought some light to your clinical
problem, which is frequently encountered, and requires particular
attention given the possibility that hypothyroxinemia in expecting mothers
may have a deleterious role for the progeny's final IQ (see Haddow, Pop,
etc). Furthermore, the fact your patient already had a serum TSH of 3.6 mU/L
in the first trimester (while taking 150 mcg) is an indication that she
was slightly undertreated for this stage of early pregancy. It is
therefore not surprizing that a few weeks later the TSH rose to 26 mU/L.
As I indicated above, you "ran behind the cat", and this can be
shown by the fact that, at 6 months of gestation, the serum TSH was still
too high (4.6 mU/L), despite giving 250 mcg/day.
Prof Daniel GLINOER<Daniel_GLINOER@stpierre-bru.be>