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Ines Bucci Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), G.d’Annunzio University Chieti-Pescara, Chieti, Italy
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Giulia Di Dalmazi Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Cesidio Giuliani Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), G.d’Annunzio University Chieti-Pescara, Chieti, Italy

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Paola Russo Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Beatrice Ciappini Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Cristina Amatetti Medical Oncology, Santo Spirito Hospital, Pescara, Italy

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Pierre Guarino Otorhinolaryngology Head and Neck Surgery Unit, Santo Spirito Hospital, Pescara, Italy

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Giorgio Napolitano Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), G.d’Annunzio University Chieti-Pescara, Chieti, Italy
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Summary

We report the case of an 88-year-old man hospitalized for COVID-19 with persistently very high procalcitonin (proCt) levels despite infection resolution. Since proCt is an adjunct tumor marker in the diagnosis of medullary thyroid carcinoma (MTC), serum calcitonin (Ct) was also measured showing very high levels. Computed tomography (CT) scan showed the presence of a thyroid mass and neck ultrasound revealed a solid isoechoic, inhomogeneous, 50 mm nodule in the right thyroid lobe, extended into the mediastinum. Fine needle aspiration (FNA) of the thyroid nodule confirmed the diagnosis of MTC. An 18F-fluorodopa positron emission tomography/computed tomography (PET/CT) scan revealed the presence of distant metastases in ribs, vertebrae, in the right iliac wing and the liver. Since surgery was not feasible, the patient was started on cabozantinib 40 mg/dL. After 16 months the patient is still on cabozantinib at the same dose, he reports complete autonomy in daily life activities, and serum Ct is still elevated; however, the imaging evaluation does not show signs of disease progression.

Learning points

  • High procalcitonin serum values despite the absence of infection are suggestive of MTC.

  • Advanced MTC with multiple metastases can have an indolent course and can go unrecognized for years.

  • Cabozantinib is a valuable option for the treatment of advanced MTC.

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Ines Bucci Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST) G. d’Annunzio University Chieti-Pescara, Chieti, Italy
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Cesidio Giuliani Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST) G. d’Annunzio University Chieti-Pescara, Chieti, Italy

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Giulia Di Dalmazi Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Daniele Intraina Neurosurgery Unit, Ospedale Santo Spirito, Pescara, Italy

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Donato Zotta Neurosurgery Unit, Ospedale Santo Spirito, Pescara, Italy

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Alfio Ieraci Pathology Unit, Ospedale Santo Spirito, Pescara, Italy

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Livio Presutti Department of Otolaryngology – Head and Neck Surgery, IRCCS Azienda Ospedaliero – Universitaria, Bologna, Italy

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Giorgio Napolitano Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST) G. d’Annunzio University Chieti-Pescara, Chieti, Italy
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy

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Summary

Brain metastases as the first clinical presentation of a papillary thyroid carcinoma (PTC) are exceptional, while cavernous angiomas are common cerebral malformations. We report the case of a 36-year-old male with an incidental brain lesion mimicking a cavernous angioma on MRI. Gamma knife radiosurgery was performed, but after 6 months, the patient developed neurological symptoms, and a repeat brain MRI revealed a significant increase in the mass. The patient underwent neurosurgery, and the histological examination of the lesion revealed metastatic carcinoma of thyroid origin. PET–CT and neck ultrasound, subsequently performed, were concordant for the presence of a right lobe nodule and ipsilateral lymph nodes, both with ultrasound features suspicious of malignancy. Total thyroidectomy with central and right lateral neck dissection was performed, and histology confirmed an intrathyroidal multifocal PTC with lymph node metastases. Postoperative radioiodine was administered, and focal uptake within the thyroid bed, without distant metastases or brain remnants, was found on the post-therapeutic whole-body scan. At 2 years from diagnosis, the patient is in good health and undergoes clinical and imaging follow-up.

Learning points

  • Brain cavernous angiomas are common cerebral vascular malformations that are usually diagnosed by MRI.

  • Despite the high accuracy of MRI, the exam is not pathognomonic, and misdiagnosis cannot be excluded.

  • Brain metastases from PTC are very rare; however, they can mimic a cavernous angioma. Therefore, the differential diagnosis should always be considered.

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Maxim John Levy Barnett Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA

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Carlo Casipit Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA

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Sri Ram Teja Sathi Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA

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Ana Del Carmen Rivadeneira Rodriguez Jefferson Einstein Hospital, Philadelphia, Pennsylvania, USA

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Summary

Thyroid storm is a clinical diagnosis characterized by life-threatening multisystemic organ involvement in the setting of uncontrolled hyperthyroidism. Current estimates suggest a mortality rate of up to 30%. Treatment often consists of the administration of thionamide medications, iodine solution(s), corticosteroids, and beta-blockers; in extreme circumstances, both plasmapheresis and thyroidectomy are subsequent therapeutic options. Thionamides are typically administered orally, with the intent of preventing further thyroid hormone synthesis; however, in the literature, there are instances whereby oral access cannot be obtained, and alternative routes of administration are required. We present a case of a patient who presented with a thyroid storm due to lack of adherence to methimazole. During admission, he was found to have significant abdominal pain and ultimately a duodenal perforation requiring strict nil-per-os (NPO) status, due to which he was unable to receive oral thionamides. Due to the lack of availability of intravenous formulations of thionamides in the United States, this patient was treated with an enema compound of propylthiouracil for a total of five per rectum (PR) doses. He would later develop hepatocellular injury, requiring discontinuation and eventual transition to oral methimazole. The literature pertaining to alternative-route thionamide administration is scant, and therefore this case report and literature review is written to provide an up-to-date review and further educate all levels of clinicians about this infrequent (but emergent) situation.

Learning points

  • Thyroid storm is a clinical diagnosis for which urgent recognition is required to prevent untoward mortality.

  • Treatment for thyroid storm requires prompt administration of thionamides, iodine, corticosteroids, and beta-blockers. In extreme circumstances, treatment considerations include plasmapheresis and thyroidectomy.

  • Infrequently, patients with a thyroid storm may not be able to tolerate oral medications, for which alternative routes of access are required.

  • Currently, available alternatives include intravenous methimazole (in Europe and Japan), as well as both enema and suppository preparations of propylthiouracil and methimazole.

Open access
Cristian Petolicchio Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

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Sara Brasili Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy

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Stefano Gay Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy

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Francesco Cocchiara Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy

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Irene Campi Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy

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Luca Persani Department of Endocrine and Metabolic Diseases, IRCCS Istituto Auxologico Italiano, Milan, Italy

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Lara Vera Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy

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Diego Ferone Endocrinology Unit, IRCCS Ospedale Policlinico San Martino, Genoa, Italy
Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy

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Federico Gatto Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy

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Summary

The resistance to thyroid hormone syndrome (RTHβ) occurs uncommonly and requires a high level of clinical suspicion and specific investigations to reach a precise diagnosis and to avoid unnecessary and potentially harmful therapies. We report a case of a young male patient referred to our unit for SARS-CoV-2 infection and atrial fibrillation with elevated thyroid hormones and non-suppressed thyroid-stimulating hormone (TSH), for which antithyroid therapy was prescribed. A mood disorder was reported in the medical history. The family history was unknown as the patient was adopted. Thyroid-specific antibodies were undetectable, and thyroid ultrasound revealed a normal thyroid gland without nodules. After the resolution of SARS-CoV-2 infection, the diagnostic workup continued, and the pituitary MRI revealed a small area ascribable to a microadenoma. Due to atrial fibrillation, the execution of the T3 test was contraindicated. The octreotide long-acting release (LAR) test showed an initial reduction of free thyroid hormones levels at first administration, which was consistent with the presence of a TSH-secreting pituitary tumour, although an escape from the response was observed after the following two injections of octreotide LAR. Indeed, the genetic investigation revealed a variant in heterozygosity of the THRβ gene (Pro453Ser), thus leading to an RTHβ diagnosis, and, therefore, medical treatment with triiodothyroacetic acid was initiated. After 2 years from the SARS-CoV-2 infection, the patient continues the follow-up at our outpatient clinic, and no other medical interventions are needed.

Learning points

  • RTHβ is a rare genetic syndrome characterised by discrepant thyroid function tests and by a dissociation between the observed hormone levels and the expected patient signs and symptoms.

  • Features of thyroid hormone deficiency in TR-ß dependent tissues (pituitary gland, hypothalamus, liver and neurosensitive epithelia), as well as thyroid hormone excess in TR-α-dependent tissues (heart, bone, skeletal muscle and brain), may coexist in the same individual.

  • Clinical pictures can be different even when the same variant occurs, suggesting that other genetic and/or epigenetic factors may play a role in determining the patient’s phenotype.

  • Differentiating RTHβ from a TSH-secreting pituitary tumour is very difficult, especially when a concomitant pituitary adenoma is detected during diagnostic workup. The injection of long-acting somatostatin analogues can help differentiate the two conditions, but it is important to detect any interference in the dosage of thyroid hormones to avoid an incorrect diagnosis.

  • Genetic testing is fundamental to prevent unnecessary and potentially harmful therapies.

  • Medical treatment with triiodothyroacetic acid was demonstrated to be effective in reducing thyroid hormone excess and controlling symptoms.

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Tejal Patel Division of Endocrinology, Children’s National Hospital, Washington, District of Columbia, USA

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Rachel Longendyke Division of Endocrinology, Children’s National Hospital, Washington, District of Columbia, USA

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Roopa Kanakatti Shankar Division of Endocrinology, Children’s National Hospital, Washington, District of Columbia, USA
Department of Pediatrics, George Washington School of Medicine, Washington, District of Columbia, USA

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Nadia Merchant Division of Pediatric Endocrinology, University of Texas Southwestern Medical Center, Dallas, Texas, USA

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Summary

Iodine nutrition is a growing issue within the USA due to newer trends of non-iodized salts. There are no recent reviews looking at the current state of iodine deficiency-induced hypothyroidism in children in the USA. We performed a retrospective chart review at our tertiary pediatric endocrine clinic; four met the diagnostic criteria for iodine deficiency defined by a low urine iodine level. We further characterized severity of disease, risk factors, goiter, thyroid labs and antibodies. All cases had significant goiter and were diagnosed within the last 2 years. One case had iodine deficiency due to no iodized salt intake along with concurrent diagnosis of developmental delay and multiple food allergies, while others involved the use of non-iodized salts. Two cases had iodine deficiency along with autoimmunity. It is critical to obtain a dietary history for all patients who present with goiter and/or hypothyroidism. There may be a need to consider reevaluating current preventative measures for iodine deficiency, especially for certain vulnerable populations such as children who do not consume iodized salt.

Learning points

  • In recent decades, iodine nutrition has become a growing concern due to changing dietary patterns and food manufacturing practices.

  • A dietary history is crucial to obtain in children presenting with hypothyroidism and goiter, especially in children with restrictive diets due to behavioral concerns, developmental delays, or multiple food allergies.

  • Of the 12 different types of salts commercially available, only table salt contains iodine in an appropriate amount; thus, individuals using specialty salts can develop mild to moderate iodine deficiency-related thyroid disease.

Open access
R K Dharmaputra Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia
Gold Coast Hospital and Health Service, Gold Coast, Cairns, Queensland, Australia

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C M Piesse Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia

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S Chaubey Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia

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A K Sinha Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Endocrinolgy and Diabetes, Cairns Hospital, Cairns, Queensland, Australia
Cairns Diabetes Centre, Cairns, Queensland, Australia

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H C Chiam Cairns and Hinterland Hospital and Health Service, Cairns, Queensland, Australia
Department of Surgery, Cairns Hospital, Cairns, Queensland, Australia

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Summary

A 48-year-old Asian male, presented to the hospital for an elective total thyroidectomy in the context of 6.3 cm thyroid nodule. The fine needle aspiration cytology of the nodule confirmed papillary thyroid cancer (PTC) with some atypical histiocytes. He has a history of idiopathic arginine vasopressin deficiency (AVP-D) and has been taking oral DDAVP 100 µg daily, self-adjusting the dose based on thirst and polyuria. Additionally, he also has a history of recurrent spontaneous pneumothorax. His total thyroidectomy was aborted due to significant intraoperative bleeding, and his admission was further complicated by post-operative hyponatraemic seizure. Thyroid histology revealed the diagnosis of Langerhans cell histiocytosis (LCH), and further investigation with contrast CT demonstrated multi-organ involvement of the thyroid, lungs, and bones.

Learning points

  • Langerhans cell histiocytosis (LCH) is a condition that can affect one or more organ systems, including the pituitary, where it can present as AVP deficiency. Strict monitoring of fluid balance, as well as serial monitoring of serum sodium, is essential in all patients with AVP-D in the perioperative setting.

  • Iatrogenic hyponatraemic seizure is an uncommon but serious complication of DDAVP treatment in hospitalised patients with AVP-D. DDAVP dosing must be carefully monitored.

  • LCH with multisystem involvement is an important mimic for metastatic conditions, and histological diagnosis is essential to guide treatment and prognosis.

  • Although LCH without bone marrow involvement is unlikely to increase the risk of bleeding, its effect on tissue integrity may make surgery more challenging.

  • BRAF-V600E mutation is an important driver mutation and a potential therapeutic target in the treatment of LCH.

Open access
Stephanie Patrick Division of Endocrinology, Department of Medicine, The University of Tennessee, Memphis, Tennessee, USA

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Deirdre James Division of Endocrinology, Department of Medicine, The University of Tennessee, Memphis, Tennessee, USA

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Summary

Thyroid cancer is one of the most common manifestations of Cowden syndrome, yet the syndrome is rare. The incidence of Cowden syndrome is 1 in 200,000. The diagnosis can be made clinically when patients present with a combination of symptoms such as mucocutaneous lesions with a strong personal or family history of thyroid, breast, endometrial, and colorectal cancer. A high index of suspicion is required to provide a clinical diagnosis utilizing major and minor criteria. Once a clinical diagnosis is made, genetic testing for a PTEN mutation, a tumor suppressor gene, is recommended. Cancer surveillance should be performed for those with positive genetic testing as well as those with negative genetic testing who still meet clinical diagnostic criteria. We present two cases of Cowden syndrome: one case involving an increasing number of thyroid nodules in a patient with known Cowden syndrome and another patient with a strong family history of cancer, personal history of follicular thyroid cancer, and numerous colonic polyps on screening colonoscopy. These cases demonstrate how early diagnosis of Cowden syndrome can help detect early cancer in both the patient and affected relatives.

Learning points

  • Diagnosing Cowden syndrome helps pre-risk stratification for early cancer screening.

  • The diagnosis of Cowden syndrome can be made with a combination of major and minor criteria: any two major criteria with or without a minor criterion; one major and one minor criterion; or three minor criteria.

  • Patients who meet the diagnostic criteria for Cowden syndrome should undergo genetic screening.

Open access
Vahab Fatourechi Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic, Rochester, Minnesota, USA

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Amy A Swanson Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA

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Robert A Lee Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA

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Summary

We report the case of a male patient with papillary thyroid cancer, familial thoracic aortic aneurysm and dissection, and a variation in the MYH11 gene. Because of considerable tumor bulk in the neck that was not resectable, the patient underwent partial resection at age 14 years. Since then, the patient has received only suppressive thyroid hormone therapy. He is now 71 years old, which is 57 years after the initial resection. The patient received care at our institution from July 2009 to August 2019, during which we documented the stability of multiple calcified masses in the neck. Follow-up examinations at another institution from September 2019 to April 2023 also confirmed the stability of the masses. The underlying cause of this unusually long indolent course of the disease is unclear. Whether extensive tumor calcifications or the MYH11 sequence variation contributed to the disease course is also uncertain.

Learning points

  • Papillary thyroid cancer with neck metastases may, in some cases, be stable and remain asymptomatic for decades.

  • If locoregional stability of papillary thyroid cancer is documented for many years, observation may be preferable to extensive neck surgery in selected cases.

  • This is the first report of an MYH11 gene alteration and thoracic aortic aneurysm in a patient with papillary thyroid cancer with indolent neck metastases.

  • Future studies of MYH11 gene alterations in thyroid carcinoma are needed.

Open access
Yu Arai Department of Family & General Medicine, Tokyo-Kita Medical Center, Japan

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Satoru Okada Department of Family & General Medicine, Tokyo-Kita Medical Center, Japan

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Taiju Miyagami Department of General Medicine, Faculty of Medicine, Juntendo University, Tokyo, Japan

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Narumi Sue Department of Family & General Medicine, Tokyo-Kita Medical Center, Japan

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Chisato Kainaga Department of Family & General Medicine, Tokyo-Kita Medical Center, Japan

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Summary

Myxoedema coma is a severe form of hypothyroidism with multiple organ dysfunction, characterised by an altered state of consciousness and hypothermia. Intravenous thyroid hormone replacement therapy is the preferred treatment for myxoedema. The mortality rate associated with this disease is high, and early detection and intervention are essential. Supraglottal myxoedema is a rare form of periglottic oedema and can be fatal. A previously healthy 66-year-old man presented with impaired consciousness, hypothermia, and nonpitting oedema. Blood tests revealed the presence of hypothyroidism and respiratory acidosis. He was intubated for type 2 respiratory failure; however, severe laryngeal oedema made the procedure difficult to perform. Oral thyroid hormone therapy was initiated under the diagnosis of myxoedema coma. Tracheostomy was performed because of prolonged type 2 respiratory failure and laryngeal oedema. Three weeks after admission, the patient was weaned off the ventilator. Approximately a week later, laryngeal oedema improved, and the tracheostomy tube was removed. The patient was discharged and remained stable for 3 months. This case report describes a patient with comatose myxoedema and supraglottic oedema who was successfully treated with oral medication alone. This case shows that supraglottic oedema should be considered even in the absence of wheezing or other signs of upper airway obstruction.

Learning points

  • Myxoedema coma is a differential diagnosis of respiratory acidosis.

  • In myxoedematous coma, the possibility of difficult intubation due to supraglottic oedema should be considered.

  • Tracheostomy should be considered for supraglottic myxoedema, which often results in prolonged ventilator use.

  • Supraglottic myxoedema can be treated with oral medications.

Open access
John J Orrego Department of Endocrinology and Metabolism, Kaiser Foundation Health Plan of Colorado, Denver, Colorado, USA

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Joseph A Chorny Department of Pathology, Kaiser Foundation Health Plan of Colorado, Denver, Colorado, USA

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Summary

Unlike medullary thyroid carcinomas, follicular cell-derived thyroid malignancies have rarely been associated with paraneoplastic endocrine syndromes. An ultrarare case of a middle-aged man with heavily treated broadly metastatic radioactive iodine-refractory widely invasive Hürthle cell carcinoma (HCC) of the thyroid with two synchronous paraneoplastic endocrine syndromes, T3 thyrotoxicosis and hypercalcemia of malignancy, is discussed here. The levothyroxine-induced T3 thyrotoxicosis was a gradual process that became more noticeable as the tumor burden, refractory to different modalities of therapy, expanded. The 1,25-dihydroxyvitamin-D-mediated hypercalcemia, on the other hand, developed in a manner of weeks, as it usually happens. It is important to emphasize that in patients with metastatic Hürthle cell and follicular carcinomas of the thyroid, on TSH suppressive therapy, the unexplained and progressive decline in FT4 and rise in FT3 levels, resulting in an elevated FT4/FT3 ratio, could be an indication of augmented type 1 (D1) and/or type 2 (D2) deiodinase expression in tumoral tissue, causing an increased conversion from the prohormone T4 into the active metabolite T3 via outer ring deiodination.

Learning points

  • Albeit extremely rare, some patients with thyroid cancer can present with more than one concomitant paraneoplastic syndrome.

  • Although medullary thyroid carcinoma is the thyroid malignancy that is usually associated with paraneoplastic endocrine syndromes, follicular cell-derived thyroid cancers have been rarely described as being the culprit.

  • In patients with metastatic Hürthle cell and follicular thyroid carcinomas, the unexplained and progressive decline in FT4 and rise in FT3 levels could be an indication of augmented type 1 (D1) and/or type 2 (D2) deiodinase expression in tumoral tissue, causing an increased conversion from T4 into T3 leading to T3 thyrotoxicosis.

Open access