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Open access

Mauro Boronat

Summary

Isolated, adult-onset central hypothyroidism is very rare, and its diagnosis can be challenging. A 42-year-old patient was referred for evaluation of a 2.8 cm thyroid nodule. She referred symptoms that could be attributed to hypothyroidism and thyroid tests showed low TSH and normal-low levels of free T4. However, evaluation of the remaining pituitary hormones and pituitary MRI were normal, yet a radionuclide scanning revealed that the thyroid nodule was ‘hot’ and the tracer uptake in the remaining thyroid tissue was suppressed. Interpretation of these studies led to a misdiagnosis of subclinical hyperthyroidism and the patient was treated with radioiodine. Soon after treatment, she developed a frank hypothyroidism without appropriate elevation of TSH and the diagnosis of central hypothyroidism was made a posteriori. Long term follow-up revealed a progressive pituitary failure, with subsequent deficiency of ACTH and GH. This case should alert to the possibility of overlooking central hypothyroidism in patients simultaneously bearing primary thyroid diseases able to cause subclinical hyperthyroidism.

Learning points:

  • Although rarely, acquired central hypothyroidism can occur in the absence of other pituitary hormone deficiencies.
  • In these cases, diagnosis is challenging, as symptoms are unspecific and usually mild, and laboratory findings are variable, including low, normal or even slightly elevated TSH levels, along with low or low-normal concentrations of free T4.
  • In cases with low TSH levels, the coexistence of otherwise common disorders able to cause primary thyroid hyperfunction, such as autonomous nodular disease, may lead to a misdiagnosis of subclinical hyperthyroidism.
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

Marina Yukina, Nurana Nuralieva, Maksim Solovyev, Ekaterina Troshina and Evgeny Vasilyev

Summary

Insulin autoimmune syndrome (Hirata’s disease) is a disorder caused by development of autoantibodies to insulin and manifested by hypoglycaemic syndrome. The overwhelming majority of physicians do not include it in the differential diagnosis of hypoglycaemic states because of a misconception of an extremely low prevalence of this condition. This results in unnecessary drug therapy and unjustified surgical interventions in patients that otherwise would be successfully treated conservatively. This disease is strongly associated with certain alleles of the HLA gene. In most cases, this condition develops in predisposed individuals taking drugs containing sulfhydryl groups. Formation of autoantibodies to insulin may be observed in patients with other autoimmune disorders, as well as in those with multiple myeloma or monoclonal gammopathy of undetermined significance. This paper presents the first Russian case report of insulin autoimmune syndrome in an adult patient.

Learning points:

  • Insulin autoimmune syndrome, Hirata’s disease, anti-insulin antibodies, and hypoglycaemia.
Open access

Shanika Samarasinghe, Simge Yuksel and Swati Mehrotra

Summary

We report a rare case of concurrent medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC) with intermixed disease in several of the lymph node (LN) metastases in a patient who was subsequently diagnosed with clear cell renal cell carcinoma (RCC). A 56 year old female presented with dysphagia and was found to have a left thyroid nodule and left superior cervical LN with suspicious sonographic features. Fine needle aspiration biopsy (FNAB) demonstrated PTC in the left thyroid nodule and MTC in the left cervical LN. Histopathology demonstrated multifocal PTC with 3/21 LNs positive for metastatic PTC. One LN in the left lateral neck dissection exhibited features of both MTC and PTC within the same node. In the right lobe, a 0.3 cm focus of MTC with extra-thyroidal extension was noted. Given persistent calcitonin elevation, a follow-up ultrasound displayed an abnormal left level 4 LN. FNAB showed features of both PTC and MTC on the cytopathology itself. The patient underwent repeat central and left radical neck dissection with 3/6 LNs positive for PTC in the central neck and 2/6 LNs positive for intermixed PTC and MTC in the left neck. There was no evidence of distant metastases on computed tomography and whole body scintigraphy, however a 1.9 x 2.5 cm enhancing mass within the right inter-polar kidney was discovered. This lesion was highly suspicious for RCC. Surgical pathology revealed a 2.5 cm clear cell RCC, Fuhrman grade 2/4, with negative surgical margins. She continues to be observed with stable imaging of her triple malignancies.

Learning points:

  • Mixed medullary-papillary thyroid neoplasm is characterized by the presence of morphological and immunohistochemical features of both medullary and papillary thyroid cancers within the same lesion. Simultaneous occurrence of these carcinomas has been previously reported, but a mixed disease within the same lymph node is an infrequent phenomenon.
  • Prognosis of mixed medullary-papillary thyroid carcinomas is determined by the medullary component. Therefore, when PTC and MTC occur concurrently, the priority should be given to the management of MTC, which involves total thyroidectomy and central lymph node dissection.
  • Patients with thyroid cancer, predominantly PTC, have shown higher than expected rates of RCC. To our knowledge, this is the first report describing the combination of MTC, PTC, and RCC in a single patient.
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

Anna Popławska-Kita, Marta Wielogórska, Łukasz Poplawski, Katarzyna Siewko, Agnieszka Adamska, Piotr Szumowski, Piotr Myśliwiec, Janusz Myśliwiec, Joanna Reszeć, Grzegorz Kamiński, Janusz Dzięcioł, Dorota Tobiaszewska, Małgorzata Szelachowska and Adam Jacek Krętowski

Summary

Papillary thyroid gland carcinoma is the most common type of malignancy of the endocrine system. Metastases to the pituitary gland have been described as a complication of papillary thyroid cancer in few reported cases since 1965. We report the case of a 68-year-old female patient with a well-differentiated form of thyroid gland cancer. Despite it being the most common malignant cancer of the endocrine system, with its papillary form being one of the two most frequently diagnosed thyroid cancers, the case we present is extremely rare. Sudden cardiac arrest during ventricular fibrillation occurred during hospitalization. Autopsy of the patient revealed papillary carcinoma of the thyroid, follicular variant, with metastasis to the sella turcica, and concomitant sarcoidosis of heart, lung, and mediastinal and hilar lymph nodes. Not only does atypical metastasis make our patient’s case most remarkable, but also the postmortem diagnosis of sarcoidosis makes her case particularly unusual.

Learning points:

  • The goal of presenting this case is to raise awareness of the clinical heterogeneity of papillary cancer and promote early diagnosis of unexpected metastasis and coexisting diseases to improve clinical outcomes.
  • Clinicians must be skeptical. They should not fall into the trap of diagnostic momentum or accept diagnostic labels at face value. Regardless of the potential mechanisms, clinicians should be aware of the possibility of the coexistence of thyroid cancer and sarcoidosis as a differential diagnosis of lymphadenopathy.
  • This case highlights the importance of the diagnostic and therapeutic planning process and raises awareness of the fact that one uncommon disease could be masked by another extremely rare disorder.
Open access

Lorena Arnez and Victor Lawrence

Summary

A 40-year-old woman was hospitalised at 25-week gestation following a diagnosis of severe symptomatic hypercalcaemia (adjusted serum calcium 3.02 mmol/L). A diagnosis of primary hyperparathyroidism (PHP) was made on the basis of elevated parathyroid hormone (PTH) 11.2 pmol/L (reference range 1.5–6.9) and exclusion of familial hypocalciuric hypercalcaemia. Ultrasound examination of the neck did not convincingly demonstrate an abnormal or enlarged parathyroid gland and parathyroid scintigraphy was not performed due to maternal choice relating to perceived radiation risk to the foetus. At neck exploration during the 28th week of pregnancy a right lower pole parathyroid lesion was excised together with two abnormal lymph nodes (largest 1.6 cm). Histology confirmed a parathyroid adenoma and also papillary thyroid carcinoma deposits in the two resected lymph nodes. Post-operatively, levels of adjusted serum calcium normalised and pregnancy progressed uneventfully to term. Total thyroidectomy was performed 2 weeks after delivery revealing two small foci of papillary micro-carcinoma (largest 2.3 mm, one in each thyroid lobe) with no evidence of further metastatic tumour in lymph nodes removed during functional neck dissection. Radioiodine remnant ablation (RRA) was performed 2 months post thyroidectomy to allow for breast involution. The patient remains in full clinical and biochemical remission 9 years later. We present and review the difficult management decisions faced in relation to the investigation and treatment of PHP in pregnancy, further complicated by incidentally discovered locally metastatic pT1aN1aM0 papillary thyroid carcinoma.

Learning points:

  • PHP may have serious consequences during pregnancy and usually requires surgical management during pregnancy to reduce the risk of maternal and foetal complications. The indications for and optimal timing of surgical management are discussed.
  • Localisation by parathyroid scintigraphy is controversial during pregnancy: modified dose regimes may be considered in preference as an alternative to unguided neck exploration.
  • Breastfeeding is contraindicated for 6–8 weeks before radioactive-iodine remnant ablation (RRA) to prevent increased breast uptake. Breastfeeding is further contra-indicated until after a subsequent pregnancy.
  • Incidentally discovered differentiated thyroid carcinoma (DTC) in cervical lymph nodes in some cases may be managed expectantly because in one quarter of thyroidectomies the primary tumour remains occult.
Open access

C Greco, G Brigante, E Taliani, S Corrado, M Simoni and B Madeo

Summary

A 74-year-old man was referred to the Endocrinology Unit because of multinodular goiter. The dominant nodule (1.7 × 1.9 × 2.4 cm), at the medium-superior third of the left lobe, was inhomogeneously hypoechoic, with irregular margins, macrocalcifications and intranodular vascularization. Fine-needle aspiration biopsy (FNAB) was performed. The cytological diagnosis was TIR 2, benign, according to the 2013 Italian thyroid cytology classification system. Moderately high serum calcitonin (s-Ct) (61.5 pg/mL, n.r. 0–7.5) and normal CEA were detected. The Ct level in FNAB wash-out fluid (Ct-FNAB) was 1450 pg/mL. Based on s-Ct and Ct-FNAB levels, patient underwent total thyroidectomy. Macroscopically, a dominant circumscribed nodule of 2 ecm was described; the histological and immunohistochemical features identified medullary thyroid carcinoma (MTC) with paraganglioma (PG)-like pattern positive for Ct, CEA and chromogranin and negative for S-100 sustentacular cells (SC). Moreover, papillary carcinoma of 3 mm in the right lobe was also associated. No areas of hyperaccumulation of the tracer were documented at Ga68 PET/CT. No RET-proto-oncogene mutations were found. Post-surgery s-Ct levels were within normal range (4 pg/mL). Two years after thyroidectomy, the patient is still disease-free. We reported a case of sporadic and rare variant of MTC: this is the ninth described case of PG-like MTC. In this case, cytologically benign, the clinical suspicion arose from high Ct values at FNAB wash-out fluid. Even if clinical behavior of this variant seems indolent, additional studies are necessary to understand prognoses and predictive factors.

Learning points:

  • Several unusual histological variants of medullary thyroid carcinoma (MTC) have been described such as spindle cell, giant cell, clear cell, melanotic, squamous, angiosarcoma-like variants; even rarer is the paraganglioma (PG)-like pattern.
  • We here describe a case of medullary PG-like thyroid carcinoma in a 74-year-old man. This is a rare histological variant of MTC hardly diagnosed by cytology, since immunohistochemical investigations are necessary.
  • Measurement of calcitonin both in serum and in wash-out fluid from fine-needle aspiration could be an additional tool for an early and non-invasive identification of these variants.
Open access

Haruhiko Yamazaki, Hiroyuki Iwasaki, Nobuyasu Suganuma, Soji Toda, Katsuhiko Masudo, Hirotaka Nakayama, Yasushi Rino and Munetaka Masuda

Summary

Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare. The objective this study is to report a case of anaplastic transformation of locally advanced papillary thyroid carcinoma after treatment with lenvatinib. A 74-year-old woman consulted a local physician because of cough and bloody sputum. Thyroid cancer with tracheal invasion was suspected on computed tomography (CT) imaging, and she visited our hospital for treatment. We suspected anaplastic thyroid cancer (ATC) and core needle biopsy was performed. Histologic sections of the core needle biopsy showed that the tumor formed a papillary structure, and we diagnosed papillary thyroid carcinoma. Surgery would have been difficult, and we initiated lenvatinib at a low dose of 8 mg/day. CT on day 40 of lenvatinib treatment revealed that the thyroid tumor had shrunk remarkably. CT on day 111 revealed that tumor regrowth and tracheal invasion had been exacerbated. Core needle biopsy was performed, and histologic sections of the core needle biopsy that was performed after regrowth of the tumor showed that individual cancer cells had large, irregular nuclei, and necrosis was also observed. The immunohistochemical findings were negative for thyroglobulin, and only a few cells were positive for thyroid transcription factor 1, and we diagnosed ATC. Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma.

Learning points:

  • Anaplastic transformation of a primary thyroid tumor whose process can be followed is rare.
  • The resistance mechanism of lenvatinib in treatment for differentiated thyroid carcinoma has not been clarified.
  • Anaplastic transformation of the target lesion may be one of the causes of lenvatinib treatment failure in differentiated thyroid carcinoma.
Open access

Hui Yi Ng, Divya Namboodiri, Diana Learoyd, Andrew Davidson, Bernard Champion and Veronica Preda

Summary

Co-secreting thyrotropin/growth hormone (GH) pituitary adenomas are rare; their clinical presentation and long-term management are challenging. There is also a paucity of long-term data. Due to the cell of origin, these can behave as aggressive tumours. We report a case of a pituitary plurihormonal pit-1-derived macroadenoma, with overt clinical hyperthyroidism and minimal GH excess symptoms. The diagnosis was confirmed by pathology showing elevated thyroid and GH axes with failure of physiological GH suppression, elevated pituitary glycoprotein hormone alpha subunit (αGSU) and macroadenoma on imaging. Pre-operatively the patient was rendered euthyroid with carbimazole and underwent successful transphenoidal adenomectomy (TSA) with surgical cure. Histopathology displayed an elevated Ki-67 of 5.2%, necessitating long-term follow-up.

Learning points:

  • Thyrotropinomas are rare and likely under-diagnosed due to under-recognition of secondary hyperthyroidism.
  • Thyrotropinomas and other plurihormonal pit-1-derived adenomas are more aggressive adenomas according to WHO guidelines.
  • Co-secretion occurs in 30% of thyrotropinomas, requiring diligent investigation and long-term follow-up of complications.