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Open access

Daramjav Narantsatsral, Takagi Junko, Iwayama Hideyuki, Inukai Daisuke, Takama Hiroyuki, Nomura Yuka, Hirase Syo, Morita Hiroyuki, Otake Kazuo, Ogawa Tetsuya, and Takami Akiyoshi

Summary

Dupilumab an inhibitor of the interleukin (IL)-4R-alpha subunit is used for the treatment of allergic diseases. The patient was a 49-year-old man who received dupilumab for the treatment of severe atopic dermatitis. He presented hyperthyroidism with elevated thyroglobulin and anti-thyroid antibody negativity at 4 months after the initiation of therapy. On scintigraphy, the thyroid radioiodine uptake was low. Ultrasonography showed a diffuse hypoechoic area in the thyroid gland. A pathological study revealed lymphocytic infiltration. The administration of dupilumab was continued because of his atopic dermatitis that showed an excellent response. The patient`s hyperthyroidism changed to hypothyroidism 3 weeks later. Six months later his thyroid function normalized without any treatment. We herein describe the case of a patient with atopic dermatitis who developed painless thyroiditis under treatment with dupilumab. To the best of our knowledge, this is the first report of this event in the literature.

Learning points:

  • Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has been shown to be effective in the treatment atopic dermatitis and asthma with eosinophilia.
  • Painless thyroiditis is characterized by transient hyperthyroidism and hypothyroidism and recovery without anti-thyroid treatment.
  • This is the first report of painless thyroiditis as an adverse effect of dupilumab, although conjunctivitis and nasopharyngitis are the main adverse effects of dupilumab.
Open access

Nicolás Cruz-Dardíz, Nadyeschka Rivera-Santana, Marina Torres-Torres, Héctor Cintrón-Colón, Shayanne Lajud, Ernesto Solá-Sánchez, Michelle Mangual-García, and Alex González-Bóssolo

Summary

Lingual thyroid (LT) gland is the most common type of ectopic thyroid tissue, but it is an extremely rare presentation. We present a case of a 41-year-old Hispanic female patient complaining of dysphonia and dysphagia. As part of the evaluation, fiber optic flexible indirect laryngoscopy (FIL) was performed which revealed a mass at the base of the tongue. The morphological examination was highly suspicious for ectopic thyroid tissue and the diagnosis was confirmed with neck ultrasound and thyroid scintigraphy. Although the patient presented subclinical hypothyroidism, levothyroxine therapy was initiated with a favorable response which included resolution of symptoms and mass size reduction. Our case portrays how thyroid hormone replacement therapy (THRT) may lead to a reduction in the size of the ectopic tissue and improvement of symptoms, thus avoiding the need for surgical intervention which could result in profound hypothyroidism severely affecting the patients’ quality of life.

Learning points:

  • Benign LT and malignant LT are indistinguishable clinically and radiographically for which histopathology is recommended.
  • THRT, radioactive iodine 131 (RAI) therapy, and surgical excision are potential management options for LT.
  • THRT may lead to size reduction of the ectopic tissue and resolution of symptoms avoiding surgical intervention.
Open access

Kingsley Okolie, Daniel Chen, Raf Ghabrial, and Robert Schmidli

Summary

Multinodular goitre is not associated with eye disease, unless in a rare case of Marine–Lenhart syndrome where it coexists with Grave’s disease. Therefore, other causes of exophthalmos need to be ruled out when the eye disease is seen in a patient with multinodular goitre. Confusion can arise in patients with features suggestive of Graves’ ophthalmopathy in the absence of thyroid-stimulating hormone receptor autoantibodies and no evidence of other causes of exophthalmos. We present a case of multinodular goitre in a patient with exophthalmos which flared up after iodine contrast-based study. A 61-year-old Australian presented with a pre-syncopal attack and was diagnosed with toxic multinodular goitre. At the same time of investigations, to diagnose the possible cause of the pre-syncopal attack, computerised tomographic (CT) coronary artery angiogram was requested by a cardiologist. A few days after the iodine contrast-based imaging test was performed, he developed severe eye symptoms, with signs suggestive of Graves’ orbitopathy. MRI of the orbit revealed features of the disease. Although he had pre-existing eye symptoms, they were not classical of thyroid eye disease. He eventually had orbital decompressive surgery. This case poses a diagnostic dilemma of a possible Graves’ orbitopathy in a patient with multinodular goitre.

Learning points:

  • Graves’ orbitopathy can occur in a patient with normal autothyroid antibodies. The absence of the thyroid antibodies does not rule out the disease in all cases.
  • Graves’ orbitopathy can coexist with multinodular goitre.
  • Iodine-based compounds, in any form, can trigger severe symptoms, on the background of Graves’ eye disease.
Open access

Haruhiro Sato and Yuichiro Tomita

Summary

Resistance to thyroid hormone (RTH), which is primarily caused by mutations in the thyroid hormone (TH) receptor beta (THRB) gene, is dominantly inherited syndrome of variable tissue hyposensitivity to TH. We herein describe a case involving a 22-year-old Japanese man with RTH and atrial fibrillation (AF) complaining of palpitation and general fatigue. Electrocardiography results revealed AF. He exhibited elevated TH levels and an inappropriately normal level of thyroid-stimulating hormone (TSH). Despite being negative for anti-TSH receptor antibody, thyroid-stimulating antibody and anti-thyroperoxidase antibody, the patient was positive for anti-thyroglobulin (Tg) antibody. Genetic analysis of the THRB gene identified a missense mutation, F269L, leading to the diagnosis of RTH. Normal sinus rhythm was achieved after 1 week of oral bisoprolol fumarate (5 mg/day) administration. After 3 years on bisoprolol fumarate, the patient had been doing well with normal sinus rhythm, syndrome of inappropriate secretion of TSH (SITSH) and positive titer of anti-Tg antibody.

Learning points:

  • Atrial fibrillation can occur in patients with RTH.
  • Only a few cases have been reported on the coexistence of RTH and atrial fibrillation.
  • No consensus exists regarding the management of atrial fibrillation in patients with RTH.
  • Administration of bisoprolol fumarate, a beta-blocker, can ameliorate atrial fibrillation in RTH.
Open access

Ehtasham Ahmad, Kashif Hafeez, Muhammad Fahad Arshad, Jimboy Isuga, and Apostolos Vrettos

Summary

Primary hypothyroidism is a common endocrine condition, most commonly caused by autoimmune thyroiditis (Hashimoto’s disease) while Graves’ disease is the most common cause of hyperthyroidism. Hypothyroidism is usually a permanent condition in most patients requiring lifelong levothyroxine treatment. Transformation from Hashimoto’s disease to Graves’ disease is considered rare but recently been increasingly recognised. We describe a case of a 61-year-old lady who was diagnosed with hypothyroidism approximately three decades ago and treated with levothyroxine replacement therapy. Approximately 27 years after the initial diagnosis of hypothyroidism, she started to become biochemically and clinically hyperthyroid. This was initially managed with gradual reduction in the dose of levothyroxine, followed by complete cessation of the medication, but she remained hyperthyroid, ultimately requiring anti-thyroid treatment with Carbimazole. This case highlights that there should be a high index of suspicion for a possible conversion of hypothyroidism to hyperthyroidism, even many years after the initial diagnosis of hypothyroidism. To our knowledge, this case illustrates the longest reported time interval between the diagnosis of hypothyroidism until the conversion to hyperthyroidism.

Learning points:

  • Occurrence of Graves’ disease after primary hypothyroidism is uncommon but possible.
  • In this case, there was a time-lapse of almost 28 years and therefore this entity may not be as rare as previously thought.
  • Diagnosis requires careful clinical and biochemical assessment. Otherwise, the case can be easily confused for over-replacement of levothyroxine.
  • We suggest measuring both anti-thyroid peroxidase (TPO) antibodies and TSH receptor antibodies (TRAB) in suspected cases.
  • The underlying aetiology for the conversion is not exactly known but probably involves autoimmune switch by an external stimulus in genetically susceptible individuals.
Open access

Shigenori Nakamura, Teruyuki Masuda, and Masatoshi Ishimori

Summary

We report a case of a 15-year-old girl with a midline neck mass that was first noted 2 or 3 years previously. She had been treated with levothyroxine (L-T4) for congenital hypothyroidism until 11 years of age. Ultrasonography revealed an atrophic right thyroid (1.0 × 1.6 × 2.6 cm in size) and a mass (2.3 × 1.0 × 3.5 cm in size) in the upper part of the neck. No left lobe of the thyroid was detected. On further evaluation, Tc-99m pertechnetate thyroid scintigraphy and CT showed ectopic thyroid tissue in the lingual region and infrahyoid region. Thus, she was diagnosed as having dual ectopic thyroid and thyroid hemiagenesis. The atrophic right thyroid was thought be non-functional. Treatment with L-T4 was started to reduce the size of the dual ectopic thyroid tissue. This may be the first reported case of dual ectopic thyroid associated with hemiagenesis detected only by ultrasonography.

Learning points:

  • Ultrasonography can confirm the presence or absence of orthotopic thyroid tissue in patients with ectopic thyroid.
  • The cause of congenital hypothyroidism should be examined.
  • Clinical manifestation of ectopic thyroid may appear when the treatment with L-T4 is discontinued.
  • Annual follow-up is needed in all children when their thyroid hormone replacement is stopped.
Open access

Naoya Toriu, Masayuki Yamanouchi, Rikako Hiramatsu, Noriko Hayami, Junichi Hoshino, Akinari Sekine, Masahiro Kawada, Eiko Hasegawa, Tatsuya Suwabe, Keiichi Sumida, Toshiharu Ueno, Naoki Sawa, Kenichi Ohashi, Takeshi Fujii, Kenmei Takaichi, Motoko Yanagita, Tetsuro Kobayasi, and Yoshifumi Ubara

Summary

We report the case of a 67-year-old Japanese woman with type 1 diabetes mellitus. At 47 years of age, her hemoglobin A1c (HbA1c) was 10.0%, and she had overt nephropathy. The first renal biopsy yielded a diagnosis of diabetic nephropathy. Intensive glycemic control was initiated and her HbA1c improved to 6.0%. Renal dysfunction showed no progression for 15 years. At 62 years of age, a second renal biopsy was performed. Glomerular lesions did not show progression but tubulointerstitial fibrosis and vascular lesions showed progression compared with the first biopsy. Intensive glycemic control can prevent the progression of glomerular lesions, but might not be effective for interstitial and vascular lesions.

Learning points:

  • Intensive control of blood glucose can prevent the progression of glomerular lesions.
  • Intensive control of blood glucose may not be able to prevent progression of interstitial and vascular lesions.
  • CSII reduces HbA1c without increasing the risk of hypoglycemia.
Open access

Georgios Velimezis, Argyrios Ioannidis, Sotirios Apostolakis, Maria Chorti, Charalampos Avramidis, and Evripidis Papachristou

Summary

During embryogenesis, the thymus and inferior parathyroid glands develop from the third pharyngeal pouch and migrate to their definite position. During this process, several anatomic variations may arise, with the thyroid being one of the most common sites of ectopic implantation for both organs. Here, we report the case of a young female patient, who underwent total thyroidectomy for papillary carcinoma of the thyroid. The patient’s history was remarkable for disorders of the genitourinary system. Histologic examination revealed the presence of well-differentiated intrathyroidal thymic tissue, containing an inferior parathyroid gland. While each individual entity has been well documented, this is one of the few reports in which concurrent presentation is reported. Given the fact that both the thymus and the inferior parathyroid are derivatives of the same embryonic structure (i.e. the third pharyngeal pouch), it is speculated that the present condition resulted from a failure in separation and migration during organogenesis.

Learning points:

  • Intrathyroidal thymus and parathyroid are commonly found individually, but rarely concurrently.
  • It is a benign and asymptomatic condition.
  • Differential diagnosis during routine workup with imaging modalities can be challenging.
Open access

Pradeep Vasudevan, Corrina Powell, Adeline K Nicholas, Ian Scudamore, James Greening, Soo-Mi Park, and Nadia Schoenmakers

Summary

In the absence of maternal thyroid disease or iodine deficiency, fetal goitre is rare and usually attributable to dyshormonogenesis, for which genetic ascertainment is not always undertaken in the UK. Mechanical complications include tracheal and oesophageal compression with resultant polyhydramnios, malpresentation at delivery and neonatal respiratory distress. We report an Indian kindred in which the proband (first-born son) had congenital hypothyroidism (CH) without obvious neonatal goitre. His mother’s second pregnancy was complicated by fetal hypothyroid goitre and polyhydramnios, prompting amniotic fluid drainage and intraamniotic therapy (with liothyronine, T3 and levothyroxine, T4). Sadly, intrauterine death occurred at 31 weeks. Genetic studies in the proband demonstrated compound heterozygous novel (c.5178delT, p.A1727Hfs*26) and previously described (c.7123G > A, p.G2375R) thyroglobulin (TG) mutations which are the likely cause of fetal goitre in the deceased sibling. TG mutations rarely cause fetal goitre, and management remains controversial due to the potential complications of intrauterine therapy however an amelioration in goitre size may be achieved with intraamniotic T4, and intraamniotic T3/T4 combination has achieved a favourable outcome in one case. A conservative approach, with surveillance, elective delivery and commencement of levothyroxine neonatally may also be justified, although intubation may be required post delivery for respiratory obstruction. Our observations highlight the lethality which may be associated with fetal goitre. Additionally, although this complication may recur in successive pregnancies, our case highlights the possibility of discordance for fetal goitre in siblings harbouring the same dyshormonogenesis-associated genetic mutations. Genetic ascertainment may facilitate prenatal diagnosis and assist management in familial cases.

Learning points:

  • CH due to biallelic, loss-of-function TG mutations is well-described and readily treatable in childhood however mechanical complications from associated fetal goitre may include polyhydramnios, neonatal respiratory compromise and neck hyperextension with dystocia complicating delivery.
  • CH due to TG mutations may manifest with variable phenotypes, even within the same kindred.
  • Treatment options for hypothyroid dyshormogenic fetal goitre in a euthyroid mother include intraamniotic thyroid hormone replacement in cases with polyhydramnios or significant tracheal obstruction. Alternatively, cases may be managed conservatively with radiological surveillance, elective delivery and neonatal levothyroxine treatment, although intubation and ventilation may be required to support neonatal respiratory compromise.
  • Genetic ascertainment in such kindreds may enable prenatal diagnosis and anticipatory planning for antenatal management of further affected offspring.
Open access

Elizabeth M Madill, Shamil D Cooray, and Leon A Bach

Summary

Thyrotoxicosis is an under-recognised but clinically important complication of parathyroidectomy. We report a case of a 37-year-old man with tertiary hyperparathyroidism who initially developed unexplained anxiety, diaphoresis, tachycardia, tremor and hyperreflexia one day after subtotal parathyroidectomy. Thyroid biochemistry revealed suppressed thyroid stimulating hormone and elevated serum free T4 and free T3 levels. Technetium-99m scintigraphy scan confirmed diffusely decreased radiotracer uptake consistent with thyroiditis. The patient was diagnosed with thyrotoxicosis resulting from palpation thyroiditis. Administration of oral beta-adrenergic antagonists alleviated his symptoms and there was biochemical evidence of resolution fourteen days later. This case illustrates the need to counsel patients about thyroiditis as one of the potential risks of parathyroid surgery. It also emphasises the need for biochemical surveillance in patients with unexplained symptoms in the post-operative period and may help to minimise further invasive investigations for diagnostic clarification.

Learning points

  • Thyroiditis as a complication of parathyroidectomy surgery is uncommon but represents an under-recognised phenomenon.
  • It is thought to occur due to mechanical damage of thyroid follicles by vigorous palpation.
  • Palpation of the thyroid gland may impair the physical integrity of the follicular basement membrane, with consequent development of an inflammatory response.
  • The majority of patients are asymptomatic, however clinically significant thyrotoxicosis occurs in a minority.
  • Patients should be advised of thyroiditis/thyrotoxicosis as a potential complication of the procedure.
  • Testing of thyroid function should be performed if clinically indicated, particularly if adrenergic symptoms occur post-operatively with no other cause identified.