A Case of Thyroid cancer in Ectopic thyroid tissue (Critical analysis)

Original case by Yanery’s Agosto-VargasMadeleine GutiérrezJosé Hernán MartínezMichelleMangual-GarciaCoromoto PalermoSharon Vélez-MaymiLuis Hernández-VázquezSamayra Miranda-RodríguezAlex González-BossoloErnesto Solá-Sánchez, and Marianne Hernández-Negrón

CRITICAL REVIEW BY DR. OM J LAKHANI (ENDOCRINOLOGIST)

This is the case of a 33-year-old man without significant medical history who was incidentally diagnosed with a right neck cystic mass by computer tomography (CT) after a motor vehicle accident. Patient denied diaphoresis, palpitations, diarrhea, constipation, mood changes, or any other symptoms. Physical exam revealed a right-sided tender neck mass, without any other remarkable findings. He did not have history of neck irradiation, thyroid disease, or family history of thyroid cancer. Thyroid function tests were within normal limits (TSH: 1.5 IU/mL). Excisional biopsy of the neck mass reported metastatic, well-differentiated, thyroid papillary carcinoma within lymph node tissue. Pathologic description consisted of a nodular segment, tannish, rubbery specimen with attached membranous cystic tissue. The pathological specimen (lymph node) was distorted and had a well-defined cystic structure within it. While the cystic structure measured 2 cm × 1.5 cm × 1 cm, the lymph node measured 1.5 cm × 1 cm (Figure 2). Due to previous findings, he underwent total thyroidectomy with right neck dissection in order to rule out occult primary carcinoma of the thyroid. Histopathological findings revealed a normal thyroid gland without evidence of papillary thyroid carcinoma and sixteen right neck lymph nodes without evidence of metastasis. Thyroid pathology was meticulously reviewed, without any evidence of papillary thyroid carcinoma identified.

Q What is your impression of this case ?

It seems there is PTC present in a rare ectopic tissue present in the cervical region since the Eutopic thyroid gland has no evidence of thyroid cancer.

Q So this is a case of Papillary thyroid cancer (PTC) post thyroidectomy. Would you give post operative radioactive iodine in this case ?

All patients with PTC donot require radioactive iodine therapy post operatively.  In all such cases a post-operative re-staging is done to classify the patient into Low risk,  Intermediate risk and high risk.

Radioactive iodine therapy is indicated in those considered to have high risk according to American thyroid association (ATA) guidelines. The following are considered to be high risk

  • Gross extrathyroidal extension
  • Incomplete surgery / gross residual disease
  • Distant metastasis
  • Post op Tg suggestive of distant metastasis

It is considered in those with ‘intermediate’ risk and not indicated in those with low risk.

Q In which risk category would you classify this patient ?

It is difficult to classify the patient according to ATA classification since there is presence of PTC in the ectopic thyroid gland but not in the eutopic thyroid gland. Also there is no evidence of lymph node metastasis. Hence it would be difficult to classify this patient and hence consider the patient as having intermediate risk and CONSIDER radioactive iodine therapy for this patient.

 

Q How will you follow up this patient ?

I would not start the patient on LT4 and follow the patient after 6-8 weeks with TSH. If TSH is >30 , patient sent for Radioactive iodine ablation with 30 mCi.

After surgery, thyroid hormone replacement was started. One month after procedure, thyroglobulin was 133.61 ng/ml (1.15–130.77 ng/ml) and thyroglobulin antibodies were 11.8 uU/ml (negative, less than 45 uU/ml).

Q What is interpretation of these reports ?
We donot know if the Tg is stimulated or unstimulated, however in either case Tg is very high and needs evaluation. This would be classified as ‘Biochemical incomplete response’ or ‘Structural incomplete response’ depending on the presence or absence of any remnant tissue in the neck. So I would order a neck ultrasound from an experienced radiologist as my first line of approach.

In retrospect it suggests that the authors should have considered Radioactive iodine ablation post operatively. However, we have an advantage of hind sight and as described above the post operative staging according to ATA was tricky to begin with.

Thyroid scintigraphy reported functional thyroid remnants at the right thyroid bed. Ultrasonography evaluation revealed hypoechoic foci within the thyroid beds bilaterally, likely secondary to postsurgical granulation tissue versus residual thyroid tissue.

A right, level 2A lymph node seen measured 2.1 × 1 cm with loss of normal lymph node morphology, without microcalcifications or internal increase in vascularity. Another lymph node at level 3 measured 2 cm × 0.7 cm × 8.7 cm, without worrisome features. Fine needle aspiration biopsy of the aforementioned nodules showed papillary thyroid carcinoma.

Q How will you restage this patient now ?

The patient now is re-staged as high risk.

Q What are the treatment options now ?

For residual disease in neck the options are close follow up, surgery and radioactive iodine ablation.

In Gross extensive residual disease surgery is the best option. For minimal residual disease surgery is indicated in cases where size of lateral nodes is >1.5 cm. In this case a repeat surgery for local disease would be a better option.

Final diagnosis was malignant transformation of heterotopic thyroid tissue. Whole-body scan showed functional thyroid tissue remnants in the thyroid bed with multiple enlarged neck lymph nodes. At that time, TSH was elevated (44.3 IU/mL) and free T4 was suppressed (0.58 ng/dl; normal value: 0.75–1.54 ng/dl). The patient was referred to nuclear medicine for radioiodine therapy. Radioiodine ablation 142.2 mCi was given. After appropriate cessation of hormone replacement therapy, whole-body scan showed no nodules uptake.

Q Why this approach is incorrect to an extent ?

Presence of considerable local disease it is difficult to judge and ablate distant metastasis. Hence ideally surgery would have been a better approach followed by Radioactive iodine ablation if needed. In the currently scenario there seems to be a false reassurance of absence of distant mets on a radioactive iodine pre-therapy scan. I would advice the authors for a close post operative follow up of this case.

Learning objective.

  1. This is a rare case where PTC in an ectopic thyroid tissue that too in lateral neck region without evidence of malignancy in the eutopic thyroid.
  2. In cases where post-operative ATA staging is ambiguous, it is better to consider a higher stage than a lower stage.

 

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A case of Euthyroid Graves’ orbitopathy with negative TRAb antibody.

Original CArshiya Tabasum1, Ishrat Khan1, Peter Taylor1,2, Gautam Das1 and Onyebuchi E Okosieme1,2

A 66-year-old female presented with a 4-month history of double vision, excessive tearing, sticky feeling in the eyes, and orbital pain in all gaze directions.

Q  What is the importance of double vision in a case of suspected thyroid associated orbitopathy (TAO) ?

  • Double vision suggest involvement of extraocular muscles in case of TAO

She had no symptoms of thyroid dysfunction, did not smoke, and denied any personal or family history of thyroid disease.

She was clinically euthyroid and had no palpable goiter

Her visual acuity was 5/6 in both the eyes.

She had fullness of her eyelids on the right side with erythema below the right inferior orbital rim.

 

Q  Why is this finding important “She had fullness of her eyelids on the right side with erythema below the right inferior orbital rim”  ?

 

  • This finding suggests two things
    • The patient has eyelid swelling
    • The patient has erythema of the eyelid
  • Both of these are important points in the clinical activity score of TAO as published by EUGOGO.

 

She had right eye proptosis and diplopia on vertical gaze but with no lid lag or retraction.

Her intraocular pressures were normal and the optic discs were normal on fundoscopy.

 

Q  Which Extraocular muscle is commonly involved in TAO ?

 

  • Inferior rectus is most commonly involved followed by Medial rectus.

 

Q  What are the your differential diagnosis at this stage ?

 

  • This patient has unilateral proptosis with no lid retraction or lid lag.
  • Yet, Thyroid associated orbitopathy still remains my first differential diagnosis as it the most common cause of unilateral proptosis.
  • Apart from that Non specific orbital inflammatory syndrome (inflammatory pseudotumors) would be my second differential diagnosis
  • Orbital tumors , especially those arising from optic nerve (like optic nerve glioma) would be another differential diagnosis

 

At this point, a differential diagnosis of right inferior rectus mass and thyroid eye disease was considered.

 

Q  How will you investigate this case ?

 

  • First I would send thyroid function test with TSH Receptor antibody
  • Also I would consider doing a CT scan or the orbit.

 

 

Thyroid function test was normal: TSH 2.25 U/L (reference range 0.4–4.5), FT4 11.6pmol/L (reference range 11.0–24.0), and FT3 4.3pmol/L (reference range 2.67–7.03) (Table 1)

TRAbs and TPOAbs were negative and thyroid ultrasound scan showed no evidence of thyroid disease. TRAb measurement was performed using a commercial third-generation ELISA kit that detects both thyroid-stimulating (TSAbs) and -blocking antibodies (TBAbs) with manufacturer specificity and sensitivity of 100 and 95%, respectively, and positive cut-off of >0.4 U/L (RSR Laboratories, Cardiff, UK)

In the ELISA, serum TRAbs inhibit the binding of human biotin-labeled monoclonal antibody to immobilized recombinant TSH receptor on the ELISA plate. The amount of M22-biotin bound to the plate is then determined by the addition of streptavidin peroxidase and tetramethylbenzidine and the absorbance of the mixture is read at 450 nm using a plate reader

 

Q  What is the role of measurement of TSH receptor antibody ?

 

  • TSH receptor antibody would help in confirming the diagnosis of Graves’ disease and hence TAO
  • It will also help in assessing the severity of the disease, guide management decision and help in follow up of the patient

 

Q  How do TRAb antibodies predict the outcome of the patient with TAO ?

 

  • Higher TRAb levels at the time of diagnosis are associated with worse clinical course and poor outcomes.

 

Q  What are the subtypes of TSH receptor antibodies ?

 

  • Stimulating – TSI à Graves’ disease
  • Blocking – TBI or TBII – Atropic thyroiditis
  • Neutral

 

Q  What are the methods by which TSH receptor antibodies are tested ?

 

  • There are two major ways in which TSH Receptor antibodies are tested
  • The first is TBII assay (Receptor method) and the other is functional biological assay for TRAb.
  • TBII assay cannot differentiate between stimulating and blocking antibodies while the functional assay can differentiate between the two.

 

Q  Tell me something about TBII assay ?

 

  • TBII assay are based on the principle of TSH binding to the TSH receptor and the antibodies competing with this binding.
  • Naturally they donot distinguish between TSI and TBI (TBAbs)
  • The 2nd generation TBII assay uses radiolabelled TSH receptor for assay
  • The 3rd generation TBII assay uses recombinant TSHR and monoclonal antibody against TSI.

 

Q  Tell me about the biological assay for TRAb ?

 

  • The biological assay are based on the principle of cAMP generation on binding of ligand with TSH
  • TSI activates TSH receptor leading to generation of cAMP and TBI reduces the generation of cAMP
  • Current assays are based on Mc4-CHO cell lines
  • However interpretation of the results is sometimes difficult since the same patient may have blocking as well as stimulating antibodies.
  • Hence these are mainly used in research setting.

 

 

Q  What kind of assay is used in this case  ?

 

  • It is a TBII assay which is used
  • It would not distinguish between TSI and TBI

 

Q  What is your interpretation of the CT scan in this patient ?

 

  • The CT scan clearly shows inferior rectus thickening on both the sides.
  • Hence eventhough clinically the patient has mainly right sided proptosis, based on CT scan both the sides are involved.
  • Thickening of the EOM with sparing of the tendon insertion site is characteristic of TAO.
  • However, in this cases sparing of the tendon is not demonstrated as alternate cuts showing inferior rectus insertion are not provided.

fig1

A CT scan of the orbit showed bilateral asymmetrical enlargement of the inferior rectus, more marked on the right than on the left, and was highly suggestive of GO inflammation (Fig. 1). An MRI orbit (Fig. 2) also confirmed inflammation in keeping with GO (Fig. 2). There was no evidence of structural or other inflammatory lesions on imaging. Serum calcium and angiotensin-converting enzyme (ACE) levels were normal.

 

Q  So what is your diagnosis at end of the investigations ?

 

  • Since now there is CT evidence of bilateral involvement of the EOM, the diagnosis would most likely still be TAO.
  • Again absence of any other tumor or pathology would also favor the diagnosis of TAO, albeit euthyroid TAO.

 

Q  Since there is still no confirmed diagnosis of TAO, what would you consider doing next ?

 

  • Though this seems nothing else other than TAO based on clinical judgement, the patient being euthyroid and absence of significant elevation of TRAb antibody does create doubts about the diagnosis.
  • In option in such a case would be to perform FNAC or biopsy in such a scenario.

 

Q  What is the role of Functional imaging modalities in such cases of proptosis where diagnostic confusion exists ?

 

  • In a study done by García-Rojas et al , FDG- PET is useful for distinguishing EOM in TAO versus other conditions.
  • In their study they found that patients with TAO has higher SUVmax uptake of FDG in EOM compared to those having non thyroidal cause of EOM involvement.

 

 

Q  Assuming it is TAO, Based on the evidence provided, what is the Clinical activity score in this patient ?

 

  • The CAS would be 3 based on the evidence provided which would make it active ophthalmopathy.
  • According to the authors, the MRI is also suggestive of active inflammation.

 

Q  Describe the EUGOGO clinical activity score ?

  • EUGOGO Clinical activity score

fig2

Q  What is the severity of the TAO based on the evidence provided ?

 

  • Based on the ATA grading it would be Grade IV since there is involvement of EOM (NO SPECS classification)
  • It would be difficult to classify the patient based on the EUGOGO assessment of severity since the measurement of proptosis and severity of the soft tissue involvement is not provided.

 

She was treated symptomatically in the regional multidisciplinary Thyroid Eye Disease clinic with topical lubricants and fitted with a corrective prism. She later underwent a surgical recession of 4mm of the inferior rectus muscle with complete resolution of diplopia and headaches. A biopsy of the inferior rectus muscle taken at surgery showed a low-grade infiltrate with B and T lymphocytes. She had no further eye complaints and continued to be followed up with annual thyroid function tests.

 

Twenty-four months after initial presentation, she developed symptoms of anxiety, sweating, tremor, and palpitations. She had no goiter or eye signs. Her thyroid hormone levels were consistent with T3 toxicosis: TSH 0.04U/L, FT3 9.56mol/L, and FT4 15.5pmol/L. At this point, repeat TRAb and TPOAb measurements were positive: 7.6IU/L and 67.9IU/mL, respectively (Table 1). She was commenced on carbimazole initially and subsequently treated with a ‘block and replace’ regimen of carbimazole and levothyroxine. She responded satisfactorily with clinical and biochemical resolution and treatment was discontinued after 12 months. Her vision has since remained intact with no further disturbance of thyroid function.

 

Q  Describe the timing of diagnosis of TAO in relation with Graves’ hyperthyroidism ?

  • Timing with Graves’ hyperthyroidism
    • 20% – Precedes hyperthyroidism
    • 40%- diagnosed concurrently
    • 20%- Follows the diagnosis of hyperthyroidism
    • 20%- Occurs after Radio-active iodine therapy

 

Q  What percentage of people with TAO have hyperthyroidism, euthyroidism and hypothyroidism ?

  • With patients having TAO
    • 80%- Hyperthyroid
    • 10-20%- Euthyroid
    • 1-10%- Hypothyroid

 

Q  What are the features of Euthyroid TAO compared to hyperthyroid TAO  ?

 

  • Euthyroid TAO compared to hyperthyroid TAO are:
  • Milder
    • Less severe EOM
    • Unilateral more often
    • Lesser soft tissue involvement
    • Absence of lid lag and Upper eyelid retraction.
    • Lower degree of TRAb antibody

 

Q  What is the explanation of the absence of TRAb antibody in this case ?

 

  • Absence of TRAb antibody may be due to low titres of this antibody in case of Euthyroid graves orbitopathy.
  • The tests use for TRAb antibody donot have 100% sensitivity.
  • Antibodies against IGF-1 receptor have also been implicated in pathogenesis of TAO.

Learning points

  1. TRAb antibodies are an important test for diagnosis of TAO especially in cases of Euthyroid TAO or in cases where diagnostic confusion exists. However, in some cases of TAO, TRAb antibodies may be negative or in low titres to be detected at the time of early presentation.
  2. CT scan of the orbits is an important diagnostic tool in case of proptosis where diagnosis of TAO is not certain.
  3. FNAC, Biopsy, Surgical resection and FDG PET are other modalities used for differential diagnosis of proptosis.
  4. Onset of TAO may preceed the onset of hyperthyrodisim in patient with Graves’ disease in about 10-20% cases.

A CASE OF MEDULLARY THYROID CARCINOMA WITH A TWIST !

Original case by I Huguet et al 

A 63-year-old woman was referred to our clinic following the incidental finding of a 1 cm thyroid nodule.

Q  What tests would you order on finding the thyroid nodule ?

  1. Review the ultrasound and physical examination findings
  2. A thyroid function test
  3. FNAC of the thyroid nodule if indicated

Q  What is the indication for FNAC according to new ATA 2015 guidelines ?

 

  1. High suspicion and intermediate suspicion- FNAC if nodule > 1 cm in size
  2. Low suspicion – FNAC if nodule > 1.5 cm in size
  3. Very low suspicion- FNAC if nodule > 2 cm in size
  4. Benign – avoid FNAC

 

Q  What are the high and intermediate risk features on ultrasound for which FNAC would be indicated in this case ?

Intermediate suspicion

  1. Hypoechoic with regular margins

High suspicion

  1. Hypoechoic + one of the following:
    1. Microcalcification
    2. Irregular margins
    3. Taller than wider
    4. Extrathyroidal extension
    5. Suspicious lymph nodes
    6. Interrupted calcification

Fine-needle aspiration cytology revealed a MTC.

Q  What are typical findings of MTC on FNAC ?

 

  1. Spindle shaped cells
  2. Cells have eccentric nuclei
  3. Amyloid like material in background

Q  How will you enhance the specificity of FNAC finding ?

Use of calcitonin staining in the FNAC smear- which will confirm the diagnosis of MTC.

Subsequently, plasma calcitonin levels were found to be elevated at 84 pg/ml (normal <11.5 pg/ml).

Q  What is the cutoff used for calcitonin in patients with Thyroid nodules for diagnosis of MTC ?

 

Basal calcitonin >20 pg/ml is suggestive of MTC and Pentagastrin stimulated Calcitonin >100 pg/ml confirms the diagnosis.

There were no other abnormal findings.

Q  What other tests would you perform ?

Since this patient has MTC, there is a high possibility of patient having MEN2. I would rule out pheochromocytoma and Hyperparathyroidism. I would clinically look for mucosal neuromas and marfanoid habitus.  (though MEN2B is less likely in this case considering the age of the patient).

The presence of a co-existing phaeochromocytoma was biochemically excluded (normal urinary catecholamine and metanephrine levels). Q  What is the ideal  surgery for this patient ?

Since the patient does not have lymph nodes involvement or metastasis and Calcitonin is between 20-200 pg/ml, the guidelines suggest total thyroidectomy with prophylactic central node dissection.

The patient was subjected to total thyroidectomy with clearance of central and lateral lymph node compartments.

The pathology demonstrated a calcified 1 cm nodule consisting of polygonal cells showing positive immunostaining for chromogranin, calcitonin, S-100 and carcinoembryonic antigen (CEA; Fig. 1). The lymph nodes were clear of disease.

Q  What is the next step for the disease ?

Genetic analysis is important to ascertain family risk and person risk of MEN2.

Genetic analysis of peripheral lymphocytes of the RET oncogene (automated sequencing of the flanking exons 10, 11, 13, 14, 15 and 16) did not reveal any germline mutation.

 

Q  How will you follow up this patient ?

I would repeat the Calcitonin and CEA after 3 months.

 

The patient recovered well from the operation, but exhibited persistently elevated plasma calcitonin levels, although she remained asymptomatic. Over the following 3 years, her plasma calcitonin levels were persistently elevated, although with no clear signs of progression (106, 116, 83, 173, 212, 279 and 114 pg/ml).

Q  What is done if calcitonin is persistently high after surgery ?

  1. If it is >150 pg/ml- then imaging is done
    1. USG/CT of neck
    2. CT thorax and abdomen
    3. Bone san
  2. If <150 pg/ml- follow-up.

Since this patient has calcitonin above 150 pg/ml on several occasions, an imaging is indicated.

Her circulating CEA levels remained normal. We suspected persisting or metastatic disease, but further repeated and detailed imaging including computed tomography (CT) and magnetic resonance (MR) scanning of the neck, chest and abdomen failed to reveal any evidence of tumour. Functional imaging with radiolabelled octreotide (Octreoscan) and fluorodeoxyglucose (FDG)-positron emission tomography (PET) scanning demonstrated mild uptake of both tracers in the midline, adjacent to L2, and further CT scanning was undertaken concentrating on this area. No clear abnormality was observed, and it was concluded at this stage that the apparent uptake was due to duodenal ‘physiological tracer elimination’.

However, after 3 years, the patient was found to have developed an iron-deficiency anaemia associated with positive faecal occult blood testing. Endoscopy was undertaken, and it showed chronic atrophic gastritis with intestinal metaplasia, but in addition a large (3 cm) polyp was found in the second part of the duodenum, which was biopsied.

The duodenal biopsy showed a NET, and the patient was subsequently re-explored surgically and partial duodenectomy was performed. Pathological examination confirmed a 2.8 cm well-differentiated NET with positive immunohistochemistry for CAM5.2, ac1-AE3, enolase, chromogranin, synaptophysin and serotonin; the Ki-67 index was <2% .

Q  What does a Ki-67 of <2% suggest ?

That it is a well differentiated neuroendocrine tumor.

Q  What is done for non-metastatic well differentiated carcinoid ?

Surgery and follow up.

Surprisingly, after resection of the duodenal tumour, circulating calcitonin levels remained repeatedly undetectable, and thus the tissue was immunostained for calcitonin; this was strongly positive.

Currently, the patient remains asymptomatic with persistently undetectable serum calcitonin levels and no further anaemia. She remains with mildly elevated serum chromogranin A and gastrin levels (last determination of serum gastrin levels: 591 pg/ml, normal <40; Fig. 3), which we attribute to her chronic atrophic gastritis.

Q  Can calcitonin be produced by other NET ?

Yes. It has been reported to be produced by other neuroendocrine tumors also.  In this case the association between the two seems coincidental.

 

ENDOCRINE ROUNDS CASE 7 – ABNORMAL UTERINE BLEEDING WITH HYPOTHYROIDISM

ENDOCRINE ROUNDS CASE 7 – ABNORMAL UTERINE BLEEDING WITH HYPOTHYROIDISM

Learning Objective: Menstrual disorders and Hypothyroidism

A 35 year old Nurse came to the endocrine OPD with complaints of heavy menstrual bleeding during menstrual periods since last 4-6 months. She also had complaints of constipation on and off and generalized weakness.

She had menarche at age of 14 years. Her menses were always regular.  At present she was menstrual flow for 4 days, which are heaviest during the first 2 days. The length or her menstrual cycles is 24 days and has been the same as long as she can remember. She had similar problems about 1 year back for which she consulted a gynecologist who diagnosed her to have an ovarian cyst which ‘resolved’ with oral contraceptive pills.  The problem recurred again 4 months back.

The patient was diagnosed to have ? Subclinical hypothyroidism during her pregnancy for which she was prescribed levothyroxine. She stopped the medication on her own after delivery.

At present she is not on any medications. She works in the ICU and has shift duties. She says she has difficulty in sleeping when she is off duty. She claims she has gained a little weight since last year or so and she feels little depressed.

The patient’s mother has history of Hypothyroidism (Autoimmune). There is no family history of diabetes.

On examination she has

  1. Hirsutism (modified FG score of 10) and acne over the face
  2. Acanthosis nigricans
  3. No goiter
  4. No others signs or virilization.
  5. BMI is 23.5 kg/m2
  6. Waist circumference is 95 cm

 

She attributed her problems to the thyroid and got herself a thyroid function test which shows overt hypothyroidism. Anti TPO antibody is positive. She has Hb of 10 g/dl with microcytic hypochromic features and increased RDW

Here are the questions:

Q  Describes the attributes of a normal menstrual cycle

  • Frequency every 21 to 35 days
  • Occurs at fairly regular intervals
  • Volume of blood ≤80 mL ( < 1 tampon every 2 hours)
  • Duration is 5 days

Q  Define polymenorrhea and oligomenorrhea

  • Polymenorrhea- menstrual cycles <21 days
  • Oligomenorrhea – > 35 days

Q  What is the difference between amenorrhea and oligomenorrhea ?

Oligomenorrhea is increased length of menstrual cycle but the upper limit is not defined hence the differentiation between oligomenorrhea and amenorrhea is arbitrary. Amenorrhea is generally absence of menses for period > 3 months (some people use a cut off of 6 months) while oligomenorrhea is 35 days – 3 months or <9 cycles in a year.

Q  From a patient point of view, what is normal menstrual blood flow ?

 

  1. Need to Change tampon > 3 hours
  2. < 21 tampons required during the menstrual cycle
  3. No need to change tampon at night
  4. Patient is not anemic
  5. Clots are < 1 inch in diameter

Q  How much blood does 1 tampon soak ?

  • About 5 ml
  • A ‘super’ tampon may soak about 10 ml of blood
  • A pad may soak – 5-10 ml

Q  What is abnormal uterine bleeding ?

It refers to abnormalities of amount, duration or schedule of blood flow.

It could be either :

  1. Heavy menstrual bleed
  2. Prolonged menstrual bleed

The term menorrhagia should not be used any more

Q  What is heavy menstrual bleed ?

  1. More than 80 ml of blood flow during menstrual cycles
  2. Need to change tampon or pad every 2 hours
  3. Volume of bleeding interfering with daily activities

Q  What are some common causes of AUB is non pregnant women ?

It is given by PALM- COIEN classification

  • Polyp
  • Adenomyosis
  • Leiomyoma
  • Malignancy
  • Coagulopathy
  • Ovulatory dysfunction
  • Iatrogenic
  • Endometrial
  • Not otherwise classified

Q  What type of menstrual irregularities are seen with hypothyroidism ?

 

Women with hypothyroidism may have either oligomenorrhea or amenorrhea or Hypermenorrhea (menorrhagia)-AUB

 

Q  What is the frequency of menstrual irregularities in hypothyroidism ?

  • Evidence suggests that menstrual irregularity is less common than previously thought in patients with hypothyroidism.
  • In a study by Krassas et al
    • 77% had normal cycle
    • 16% has oligo-amenorrhea
    • 7% had hypermenorrhea
  • Oligomenorrhea and Hypermenorrhea were the most common patterns of menstrual irregularities.
  • Another study found no difference in incidence of hypermenorrhea in patients with hypothyroidism in comparison to controls. However, the same study found that patients with severe hypothyroidism were more likely to have menstrual irregularities than mild hypothyroidism. (Kakuno et al)

Q  Does the menstrual irregularity correlate with severity of hypothyroidism?

In the study quoted above, the menstrual irregularity was more common in women with overt hypothyroidism vs subclinical hypothyroidism and it did correlate with severity of hypothyroidism. However, the difference was not statistically significant.

Q  Does the presence of Anti-TPO antibody correlate with menstrual irregularities?

No.  Karassas et al did not found any difference in menstrual irregularities in patients with anti-TPO positive vs the entire group.

Q  Do the menstrual abnormalities improve with LT4 treatment?

It persists in almost half of the patients with treatment.

 

Q  What are the possible etiologies of AUB in hypothyroid patients?

 

  1. Estrogen breakthrough bleeding secondary to anovulation
  2. Decreased level of coagulation factors- VII, VIII, IX and XI seen in hypothyroid patients

Q  Is there any difference in menstrual irregularities reported from recent studies vs older studies ? If so why ?

  • Older studies showed a much higher prevalence of menstrual irregularities in hypothyroidism.
  • This was possibly due to delay in diagnosis of hypothyroidism leading to much severe symptoms

CONCLUSION

  1. Menstrual irregularities are often seen in hypothyroidism. However, prevalence of menstrual irregularities in hypothyroidism is reported less commonly in recent studies compared to older studies because of early diagnosis of hypothyroidism
  2. Oligomenorrhea is the most common menstrual irregularity reported in recent studies. Hypermenorrhea (AUB) is reported in about 7% of hypothyroid patients in comparison to 1% in controls.
  3. The menstrual irregularities may have an association with severity of hypothyroidism, but this needs more robust evidence.
  4. It has not relation with the presence of Anti-TPO antibodies.
  5. Menstrual irregularities may correct after treatment of hypothyroidism in about 50% of cases.

 

ENDOCRINE ROUNDS CASE 2- A CASE OF TOXIC ADENOMA

A 42 year old female had history of weight loss. On examination she was found to have a thyroid nodule with thyroid function test showing reduced TSH and increased T4.


We asked for a Tc99 Pertechnetate thyroid scan which is shown above.
Q. What is the interpretation of the thyroid scan report ?

It shows an autonomous hot nodule on the left lobe of thyroid. No cold nodules.

Q. What are the treatment options for this patient ?

Start the patient on Beta blockers at the time of diagnosis for symptom control.
The preferred therapy would be either surgery or radioiodine therapy. Radioiodine would be preferred over surgery as per AACE/ATA guidelines in this case considering the size of the nodule.

Q If surgery is preferred option for option, then what should be the extent of surgery in this case ?

Ipsilateral lobectomy can be done. (After ruling out absence of thyroid nodules in other lobe)

Q Will radioiodine therapy also reduce the size of the Toxic adenoma ?
Yes

Q Risk of hypothyroidism is more in Toxic adenoma compared to Graves or less ?

It is less compared to Graves as the radioactive iodine only accumluates in the toxic adenoma

Q If the patient is pretreated with carbimazole, what should be the TSH when radioiodine therapy is administered ?

It should ideally be administered when the TSH is lower (or has not normalized). In this case the damage to the normal thyroid tissue is avoided and hence post procedure hypothyroidism is avoided.

Q What is the success rate of radioiodine therapy in toxic adenoma ?

80-90%

ENDOCRINE ROUNDS CASE 1

ENDOCRINE ROUNDS CASE 1
This is a case of a middle age lady from Kashmir who came with incidentally detected thyroid nodule. A thyroid ultrasound was done, a picture of which is shown below. Thyroid function tests were suggestive of Overt hypothyroidism.

Q Ultrasound Characteristics of this lesion show Benign or malignant etiology ?
1. Doppler shows peripheral vascularity with no central vascularity
2. No visible microcalcifications
3. It is isoechoic or hyperchoic compared to surrounding area (Mixed echogenicity)
4. Regular margins
5. Spongiform appearance
6. More wide than tall (Wider > Taller)
The lesion can be characterized as ‘Low suspicion’ according to ATA 2015 guidelines
Q. What does the FNAC show ?

DR1.3
Q. What is the next step for the patient ?
1. Levothyroxine for the Overt hypothyroidism and follow up after 6 weeks
2. For the nodule- Repeat ultrasound after 6 month- If there is growth of 20% in two axis or new suspicious imaging features- Consider Repeat FNAC