Central Hypothyroidism?


Question

I am presenting a patient who I need some advice as to how I can make a diagnosis.

A 66 year old female with h/o primary hypothyroidism (TSH:7.103 in 6/01) started on synthroid 50 mcg/ day and repeat TSH was 3.318 on 8/01. Pt then was lost to f/u and the next TSH available was :12/31/02 : 0.00, pt was taken off her LT4 and repeat TSH's was :

2/28/03 : TSH :0.02 (0.34 - 5.00)

6/4/03) TSH :0.04 (0.34- 5.00)

10/6/03: TSH 0.00 (0.34 -5.00)

10/14/03: I131 uptake at 24 hours: 8.9%

12/03/03: TSH: 0.151 (0.350-5.5)

FT4: 0.86 (0.89 - 1.8)

FT3: 2.9 (2.3 - 4.2)

Pt 's only complaints are dry itchy skin and low energy.

Medications: Paxil 12.5 mg/day, lasix 20mg, provera 5mg, estrogen patch, prevacid, relfen, centrum silver and cod liver oil capsules.

Past medical history is only significant for hypertension, depression, GERD. Her physical exam is unremarkable.My working diagnosis was Central hypothyroidism.In order to evaluate the pituitary the foll tests were asked for.

1. MRI of pituitary: Normal with no masses

2. FSH: 14.8 (PT is on HRT)

3. LH: 10.3

4. Prolactin: 4.8

5. IGF :108

6. Cortisol (AM) 12.8)

In summary a 66 year old female with central hypothyroidism and normal pituitary imaging.

1. Is a TRH test indicated here.

2. Could her hypothyroidism be secondary to a hypothalamic etiology.

Thank you, Bindubal Balan , MD Bindubalbalan@aol.com

Response

Although the natural first assumption is that she has only central hypothyroidism, it seems to me that the situation is probably more complicated than that. She began with an elevated TSH, which is possible in central hypothyroidism, but it responded to treatment, she has no sign of tumor, and the rest of the evaluation is negative. Further, without treatment , her hormone levels are near normal and her RAIU is near normal (depending on Iodine supply). We do not know findings by thyroid US or antibody tests, which should be evaluated.

TRH testing would be of interest, if a good response occurred, but it often does not tell more than the basal TSH. It is rare for the TSH to be 0.00 in any situation except suppression by elevated thyroid hormone, or some sort of TSH testing error. I would guess that she has some hypothalamic/pituitary problem making her TSH set point low and easily suppressed, and this has been reported in elderly patients. This is also hard to prove. I think she also was exposed to higher than normal levels of T4 at some point so that her pituitary was suppressed.

I would follow her without treatment at this point and see if her TSH gradually return s toward normal. It would be of interest to measure TSH in a different lab to rule out some error due to heterophile antibodies. The duration of suppression of her TSH while off T4 is truly prolonged , but not incompatible with this evaluation of the problem. If the evaluation provides no further avenues of understanding, and hormone levels remain at the current level, mild T4 supplementation could be reinstituted. Please let us know any follow-up. Leslie J De Groot,MD

Neonate with Large Goiter


Question

Full term newborn male with a hx of IUGR in utero born to a mother who smoked during pregnancy but who has no hx of thyroid problems, who at birth has some respiratory distress and is noted to have a large neck mass. TSH is 775mcIU/ml and free T4 is 0.39 ng/dl so he was started on 37.5 mcg/day of synthroid then was transferred to another hosp. lat neck film shows ant displacement of the trachea and retropharyngeal fullness. CT of the neck mass showed "large heterogeneous soft tissue mass with septated and lobulated components, likely representing a goiter. enlarged thyroid lobes measure approximately 2.2 x 2 cm in cross-section, and the isthmus in the anterior neck measures 1.4 cm in width.the thyroid gland appears to extend behind the laryngopharyx at the level of the hyoid, displacing the airway anteriorly, and the carotid arteries and the jugular veins are displaced posterolaterally bilaterally. There is distortion of the tracheal cross-section, with a possible reduction in its transverse dimension." T he baby is stable on RA, has no audible stridor, but desats to 60's occasionally with feeds or agitation.

The diagnosis seems most likely to be thyroid dyshormonogenesis questions:

  1. by treating the hypothyroidism, in what percentage of cases does the goiter shrink in size? and if it does shrink, on what kind of time period would you see shrinkage(weeks, months?)?
  2. the TSH in 2 days came down to 335. most kids don't get a pertechnetate scan once started on treatment, but to prove that this truly is all thyroid tissue could we still do the scan since the TSH hasn't totally corrected?
  3. does anyone else have experience with management of a pt like this? there is reluctance on part of ent to remove the goiter because the baby is small (2.2 kg) and risk of damage to the recurrent laryngeal nerves would be high. the child's is relatively stable but if the mass doesn't shrink, he may not go home anytime soon given his occasional desats

Thank you. Dr Joyce Lee, Fellow in endocrinology, University of Michigan, joyclee@med.umich.edu

Response

-Your infant presents a most interesting and unusual problem as we rarely see goiters of this magnitude in infants these days.

In general, the most common etiology would be maternal antithyroid medicine for treatment of maternal Graves', but that does not appear to be the case in your patient. Although the mother smokes and cigarettes contain thiocyanate, I doubt that this is a factor in the absence of iodine deficiency. Nonetheless it would probably be worthwhile to ascertain the mother's dietary habits.I certainly agree that the most likely cause, therefore, is an abnormality of thyroid hormonogenesis. It would be most helpful to do a 123-I uptake and scan (rather than pertechnetate), if that were possible since by following the kinetics of the iodine release (i.e., check uptake early, then at 6 hrs and 24 hrs) you could not only verify that the swelling is thyroid, but determine whether an organification defect is present as well. Also, there is an animal model of congenital hypothyroidism in goats, I believe, that is associated with a large goiter and in which there is an abnormality of thyroglobulin synthesis. Therefore, I would certainly want to check a serum thyroglobulin level in your infant and obtain a urine sample not only for urinary iodine and creatinine but to be used for assessment of an abnormal thyroglobulin molecule as necessary as well.

If the neck swelling is thyroid, as it almost certainly is, then I would think that it should shrink relatively rapidly- days and weeks, not months, and surgery is not indicated. However, for the moment if you are concerned about the possibility of respiratory compromise because of its size, then I would push the L-T4 dose by giving an amount that brings the T4 (and free T4) to the high normal range (say 50 mcg. qd) ASAP, and then cut back to 37.5 mcg once this is achieved. I have seen TSH values normalize surprisingly quickly in infants- in a matter of 1 or 2 weeks.

I hope that these comments are helpful to you. Please feel free to contact me should you have any further questions or concerns. I would be most interested in learning about the outcome of your patient. Rosalind Brown MD,

Thyroid Carcinoma Diagnosed by Bronchoscopy


Question

I was asked to consult on a patient who felt well but went to his doc with hemoptsis. A lesion was biopsied through the bronchoscope-the diagnosis came back papillary cancer either metastatic or ectopic. The patient has been treated for several years for hypothyroidism-no local symptoms ever reported until this one episode of coughing up blood. The US of the thyroid shows two nodules left neck -neither palpable-1.5 cm posterior and 1.0 cm -isthmus no clear nodule.-Can you advise next steps? Is this likely to be locally invasive disease ? If so how is the trachea managed in such cases? What is the role for local radiation or I 131? I favor an US guided biopsy of the nodule(s) in the thyroid but the surgeon says it wont change our management. How often have you seen this? Thanks Jeffrey Sanfield MD

Sanfielj@trinity-health.org

Response

-You dont tell me the patient's age or general condition, so I will assume the person is older-50-70 and generally well.

I have seen this infrequently, fortunately, primarily with Hurthle or follicular cancers,and it always spelled big trouble. I think you must assume direct invasion as the most likely situation. Thus, while 131-I might provide a cure, prior surgical resection would be the usual program. This is a very specialized sort of surgery, with resection and re-anastomosis of the trachea as the possible approach. A surgeon at MGH has written several papers about this. Unfortunately even with this rather heroic approach, often the tumor has spread so that final outcome is not as desired.

I suggest a neck MRI and chest CAT to try to understand the situation better and see if there is bulky disease or lung mets. Assuming no obvious contraindication, then the approach might be thyroidectomy and tumor resection including probably a tracheal resection, followed by RAI scan and ablation. Let us hope that the tumor takes up RAI well.

Finally one should consider radiation, but I think this needs to be decided after operation and RAI treatment. The decision would be based on extent of disease and the resection, RAI uptake, age, histology, post-ablation TG, and possibly other factors. I would tend in this situation to favor radiation but we need the next set of data in order to think it thru.

There is a discussion of this problem in WWW.THYROIDMANAGER.ORG .

Best regards. Leslie J De Groot,MD

Sublinical Hyperthyroidism and Substernal Goiter


Question

Recent ultrasound multiple bilat nodules largest rt 2.8, left: 2.6, isthmus 3.9 cm. Extension below the suprasternal notch (new), nodules not sharply defined. A year ago he had a scan and RAIU: 6 hr 12%, 24 hr 21% . Scan inhomogeneity , cold area on left corresponding to 2.7 cm cyst on u/s, and cold area in isthmus 3.9 cm solid area , cold area on rt (1.5 cm cyst). Radiology suggested a biopsy of rt and isthmus nodules. Path: isthmus follicular lesion, favor hyperplastic nodule within nodular goiter, right nodular goiter.

I am planning to recommend surgery based on substernal extension ( do you agree?) and was wondering whether you would recommend any treatment pre-op. (i.e.: antithyroid drugs until TSH normal, or beta- blocker.) However his pulse rate is low at 60. Thank you very much, Lisa Wisniewski, MD --- lawisn@earthlink.net

Frist Response

Firstly, I would get a CAT of the chest if I was considering resection for his MNG, to be sure we know what the anatomy really is. I assume the TSH has been checked more than once, and that there has not been any recent exposure to iodine that might cause a transient episode of hyperthyroidism. So his problem is a (possibly significant) substernal extension, an FNA report that is meant to be disquieting to you although it probably is a benign lesion, and very mild hyperthyroidism which may be due to his nodules. With all of that, in a 46 year old man in presumed good health, my approach would be to recommend resection by a skilled surgeon, expecting a very easy and safe course. Probably he could be operated with a short preparation under methimazole and later added KI for a week, since the degree of hyperthyroidism is clearly minimal. If it was not for the FNA result, one could treat with RAI, and RAI is used to shrink sub-sternal goiters, a point that Dr Hennemann may comment on. Leslie J De Groot,MD

Second Response

Thanks for the opportunity to comment as well.The probability that a multinodular goiter (mng) is at an increased risk for carcinoma is controversial. My personal opinion and that of many Europeans, who have a lot of experience with this entity since it occurs frequently in Europe, is that this is most probably not the case. On the basis of this notion it is “dangerous” to do FNA for every cold nodule in such a goiter as many of these presumed benign nodules have a follicular structure. The first treatment choice in mng in Europe is administration of RAI. It is of no influence if these goiters are partially or even completely intrathoracically located. Even goiters of more than one kilogram are easily (really!) treated with RAJ. I have not treated any mng anymore with surgery since the last 20 years.

My definition of a mng is that it should be longstanding, the thyroid is mostly asymmetrical, no X irradiation to the neck in the past, no hoarse voice, no rapid growth, no suspect lymph nodes in the neck and preferably a familiar tendency for mng. Some also include the presence of a “prominent” nodule what ever that may be. If most of these points are met, I do not perform a scan neither a FNA. The treatment of choice is then RAJ.In this particular patient there are 2 aspects that deserve further consideration

  1. The patient is a male and mng is more frequently occurring in females. This point argues only weakly against the goiter being benign.
  2. The fact that a FNA has been done that shows some follicular structures, carries the consequence of surgery. The possibility however is great that there is no malignancy at all.

SUMMARIZING: Considering the approach that has been adopted in this patient and the results as a consequence of this approach, I see no other way then to operate. The reason that we in Europe are so reluctant to have mng operated is that even in experienced hands, the risk for permanent hypoparathyroidism and vocal cord paralysis is about a few percent in this continent, but may be lower in the US. Georg Hennemann, MD, PhD, FRCP, FRCP(E)

Nodules, Positive Antibodies, and Treatment?


Question

34 yr old female with multinodular goiter. She displays no symptoms and labs are

TSH 2.02 ìIU/ml

FT3 2.5 pg/ml

FT4 1.01 ng/ml

anti TPO 12.45 IU/ml

anti TG 17.49 IU/ml

TBG 194 ng/ml

Ultrasound: 3.2 x 2.1 cm nodule L, 2.1 cm nodule R as well as a 7mm nodule R

Thyroid scan w/ 274 uCi I-123 : displayed neither hot nor cold nodules. Thyroid uptake was within normal range

This patient was followed sonographically one year ago displaying a 2.8 cm nodule L and a 2.0 cm nodule R and a TSH of 1.61 IU/ml

She has been receiving levothyroxine 0.1mg for 2 weeks and her endocrinologist suggested thyroidectomy due to the nodule size. Another endocrinologist suggested FNA of both large nodules, continuation of meds and if biopsy is negative and TBG falls within normal range in three months to continue meds and ultrasound follow-up to ensure that nodule is not growing. If not thyroidectomy.

This patient also has a history of cheloid formation.

I would appreciate your opinion on the most appropriate therapeutic strategy for this atient.Thank you for your time and effort.With Regards Emily Katakis,MD,Chania General Hospital,Mournies,Chania, Crete, Greece

First Response

Dear Dr Atakis,If I may summarize this patient, then she has a multinodular goiter, is euthyroid and no cold nodules. No growth of 2 out of 3 nodules have been documented over the last year and follow up size of the smallest nodule lacks or this nodule was not seen at the second ultra sound. I assume that no suspect lymph nodes have been detected. There are no mechanical complaints.

If my summary is OK then there is no doubt in my mind that only follow up of this patient is the maximum that should be considered. If there is a family history of multinodular goiter one could be even more sure about the absence of malignancy in this goiter, but even without this suspicion for cancer is really low. I am not in favour of treatment with thyroid hormone,that caries more risks than benefits as growth is rarely reversed or inhibited but that thyrotixosis may ensue because of autonomous function of parts of the gland. Neither is there any indication for FNA or operation because suspicion for malignancy is low to absent.

If any treatment should be considered then this should be administration of radio-active iodine, but only then in the case that the thyroid becomes subclinically- (suppressed TSH but normal T4 and T3 paparameters) or full blown hyperthyroid or that serious trachea stenosis develops. In the case of tracheal deviation but no or only mild stenosis, RAI treatment is optional but not necessary. I do not understand the reasoning about TBG. I understand that this value is elevated? So what? This has nothing to do with thyroid function and FT3 and FT4 are corrected for this and I assume normal. Maybe this patient is using oestrogens or TBG maybe congenitally elevated?Georg Hennemann, MD, PhD, FRCP, FRCP

Second Response

The patient must have Hashimoto’s thyroiditis in view of the antibodies and the scan without nodules. Pseudo-nodules are common on US of Hashimoto’s glands, but usually are not distinct. Thus she may well have two thyroid diseases. In the USA, where multinodular goiter is less common (how about Crete?), I believe that in this young woman the usual approach would be to biopsy both nodules under US guidance. If benign on FNA, and they remain static and asymptomatic, and whether the final Dx is Hashimoto’s or MNG, no treatment is clearly required. However some of us still prescribe replacement ( not suppressive) doses of T4 in patients with benign nodules and MNG. The goals, especially at age 34, would be the occasional (25% of cases) reduction in size, possible help preventing further growth in lesions that are in part TSH dependent, and certain help in keeping in touch with the patient. Leslie J De Groot,MD

Amiodarone and Recurrent Graves’ Disease


Question

The patient is a 60 year old oriental lady. In 1978, age 36, this lady developed quite severe Graves' disease (non-goitrous) that failed to respond to medical treatment, and she eventually required radio-iodine treatment, which was successful, in 1979. She remained well until 1985 when she suffered a relapse, and was treated successfully on this occasion with a one year course of antithyroid medications, which we assume was carbimazole, though we do not have the old records to confirm this.

This lady subsequently remained well and euthyroid until Augusr 2001, when she developed paroxysmal ventricular tachycardia of uncertain aetiology.

Corornary angiography ruled out any significant ischaemic heart disease, and she was commenced on simvastatin 20 mg od, dipyridamole and amiodarone which was eventually reduced to 100 mg after 1 year as she had remained so stable. Her baseline pre-amiodarone TFT was : FT4 = 16.2 pmol/l, TSH = 2.2 mu/l . The TSH rose to borderline levels after about 1 year of treatment, but subsequently settled to within the normal range of 0.35 - 5.5 until recently.

She was completely well and euthyroid until around July 03, when she started to feel non-specifically unwell with fatigue and occasional palpitations. A TFT in mid September 2003 showed FT4 = 19.4, FT3= 6.7, TSH = 0.02 . During the subsequent weeks , she became gradually more symptomatic, with increased palpitations and fatigue and feeling shaky. Repeat TFT at the end of October showed FT4 = 25, FT3 = 8.9 and TSH = <0.01. TSH receptor antibodies were also found to be markedly elevated at 20 (normal <1). Anti-TPO antibodies = 219 iuml . CBC, LFT and renal function were all normal. Recurrence of Graves' disease was confirmed, and she has been commenced on carbimazole, initial starting dose 20 mg od.

The plan is now for the patient to return to her Cardiologist to discuss other treatment options than amiodarone, as her Endocrinologist recommended that the radioiodine treatment be repeated whenever possible. However, she would need to be off the amiodarone for at least 6 - 9 months before this would be feasible, as we understand thyroid iodine uptake would otherwise be very suppressed whilst she remains on this drug.

We now have a real therapeutic dilemma, as an effective treatment to avoid a recurrence of the paroxysmal VT will need to be found before amiodarone could be withdrawn. Thyroidectomy was not really recommended by her Endocrinologist, as she does not have a goitre and in addition is terrified of surgery ! As previously, I have some specific queries I would very much appreciate your and your team's comments on: Dr AT, adt_2004@yahoo.co.uk

First Response

THERE ARE 2 WAYS TO TREAT THIS PATIENT WHILE CONTINUING WITH AMIODARONE:

1. Continued co-administration of carbimazole

2. Destruction of the thyroid with ethanol injection and subsequent substitution with T4. This procedure has just been described for patients with Graves' disease and has been used for quite some years for thyroid nodules and also recently even for lymph node metastasis of thyroid carcinoma.

My suggestion would be to start with carbimazole in a titrated dosage to keep the TSH normal. You should realize that T3 and T4 parameters are often unreliable during amiodarone treatment in that values are (falsly) increased due to transport inhibition into tissues. Carbimazole can be used for many years without side effects in many patients. If serious side effects do occur so that carbimazole has to be discontinued, while it is clear that the amiodarone has to be continued, then the other option becomes into focus.

Georg Hennemann,MD

Second Response

May I offer other thoughts on this problem? Whether or not amiodarone induced this recurrence seems uncertain.. It would have been interesting to have an RAIU prior to starting carbimazole (could be zero or low), possibly IL-6 assay, and an US. It is hard to believe that the iodine load was not in some way involved, although it usually would induce hypothyroidism in patients with autoimmune thyroid disease, especially those with borderline hypothyroidism.

Be that as it may, carbimazole may well induce a remission if the amiodarone can be stopped. (Propylthiouracil might be a more interesting choice, since it would further decrease T4->T3 conversion, in contrast to carbimazole.) Some patients with amiodarone induced hyperthyrodism require addition of KClO4 (cautiously!) for a response, and of course there is a subset of patients who respond to prednisone.

Surgical resection with beta blocker preparation is a very valuable standard resort when other methods fail, and has helped us out of several difficult situations involving the fear of recurrent cardiac arythmias. The possibility of ethanol seepage outside of a small partially fibrotic, twice-treated, thyroid remnant should be kept in mind if considering what must be considered a novel treatment with ethanol. In the absence of significant published experience with this approach, I personally can not recommend it.

Leslie J De Groot,MD