Browse
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy
Search for other papers by Ines Bucci in
Google Scholar
PubMed
Search for other papers by Giulia Di Dalmazi in
Google Scholar
PubMed
Search for other papers by Cesidio Giuliani in
Google Scholar
PubMed
Search for other papers by Paola Russo in
Google Scholar
PubMed
Search for other papers by Beatrice Ciappini in
Google Scholar
PubMed
Search for other papers by Cristina Amatetti in
Google Scholar
PubMed
Search for other papers by Pierre Guarino in
Google Scholar
PubMed
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy
Search for other papers by Giorgio Napolitano in
Google Scholar
PubMed
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.
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy
Search for other papers by Ines Bucci in
Google Scholar
PubMed
Search for other papers by Cesidio Giuliani in
Google Scholar
PubMed
Search for other papers by Giulia Di Dalmazi in
Google Scholar
PubMed
Search for other papers by Daniele Intraina in
Google Scholar
PubMed
Search for other papers by Donato Zotta in
Google Scholar
PubMed
Search for other papers by Alfio Ieraci in
Google Scholar
PubMed
Search for other papers by Livio Presutti in
Google Scholar
PubMed
Endocrinology and Metabolism Unit, ASL Pescara, Pescara, Italy
Search for other papers by Giorgio Napolitano in
Google Scholar
PubMed
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.
Search for other papers by Cristian Petolicchio in
Google Scholar
PubMed
Search for other papers by Sara Brasili in
Google Scholar
PubMed
Search for other papers by Stefano Gay in
Google Scholar
PubMed
Search for other papers by Francesco Cocchiara in
Google Scholar
PubMed
Search for other papers by Irene Campi in
Google Scholar
PubMed
Search for other papers by Luca Persani in
Google Scholar
PubMed
Search for other papers by Lara Vera in
Google Scholar
PubMed
Endocrinology Unit, Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genoa, Italy
Search for other papers by Diego Ferone in
Google Scholar
PubMed
Search for other papers by Federico Gatto in
Google Scholar
PubMed
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.
Search for other papers by Stephanie Patrick in
Google Scholar
PubMed
Search for other papers by Deirdre James in
Google Scholar
PubMed
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.
Search for other papers by Vahab Fatourechi in
Google Scholar
PubMed
Search for other papers by Amy A Swanson in
Google Scholar
PubMed
Search for other papers by Robert A Lee in
Google Scholar
PubMed
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.
Search for other papers by John J Orrego in
Google Scholar
PubMed
Search for other papers by Joseph A Chorny in
Google Scholar
PubMed
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.
Search for other papers by Isabelle van Heeswijk in
Google Scholar
PubMed
Search for other papers by Antonia Ugur in
Google Scholar
PubMed
Search for other papers by Lynsey Havill in
Google Scholar
PubMed
Search for other papers by Rebecca Kinton in
Google Scholar
PubMed
Search for other papers by David Hughes in
Google Scholar
PubMed
Summary
Calciphylaxis is a rare disorder characterised by the development of painful necrotic skin lesions. Occlusion of cutaneous arterioles due to ectopic calcification leads to potentially life-threatening widespread skin loss. Most cases occur in patients with chronic renal disease, which leads to dysregulation of calcium and phosphate homeostasis. Only a handful of case reports exist describing calciphylaxis occurring in patients without chronic renal disease but with hypoparathyroidism. We report on a unique case of a 53-year-old man with multiple endocrine neoplasia type 1 syndrome and acquired hypoparathyroidism due to total parathyroidectomy who went on to develop calciphylaxis following cardiac surgery.
Learning points
-
Calciphylaxis most commonly occurs in the context of chronic renal disease but can rarely occur in its absence as a consequence of calcium and phosphate dysregulation.
-
Patients who develop necrotic skin lesions in the presence of hypoparathyroidism require an urgent dermatological opinion.
-
Mortality from calciphylaxis is high, with the majority of deaths occurring secondary to sepsis.
-
Management of calciphylaxis requires a multidisciplinary team approach to manage wound healing, infections and pain.
-
Recovery with full rehabilitation from calciphylaxis can take months to years.
Search for other papers by Andreia Amado in
Google Scholar
PubMed
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Search for other papers by Elisabete Teixeira in
Google Scholar
PubMed
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Search for other papers by Sule Canberk in
Google Scholar
PubMed
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto, R. Jorge de Viterbo Ferreira 228, 4050-313 Porto, Portugal
Search for other papers by Sofia Macedo in
Google Scholar
PubMed
Search for other papers by Bárbara Castro in
Google Scholar
PubMed
Search for other papers by Hugo Pereira in
Google Scholar
PubMed
Search for other papers by João Varanda in
Google Scholar
PubMed
Search for other papers by Susana Graça in
Google Scholar
PubMed
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Search for other papers by Amélia Tavares in
Google Scholar
PubMed
Search for other papers by Carlos Soares in
Google Scholar
PubMed
Search for other papers by Maria João Oliveira in
Google Scholar
PubMed
Search for other papers by Manuel Oliveira in
Google Scholar
PubMed
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Search for other papers by Paula Soares in
Google Scholar
PubMed
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Centro Hospitalar Universitário São João, Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Search for other papers by Manuel Sobrinho Simões in
Google Scholar
PubMed
i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, R. Alfredo Allen 208, 4200-135 Porto, Portugal
IPATIMUP - Instituto de Patologia e Imunologia Molecular da Universidade do Porto, Rua Júlio Amaral de Carvalho 45, 4200-135 Porto, Portugal
Faculdade de Medicina da Universidade do Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
Search for other papers by Antónia Afonso Póvoa in
Google Scholar
PubMed
Summary
We report a 61-year-old male patient without personal history of thyroid carcinoma or radiation exposure. In 2011, he presented with a cervical mass whose biopsy diagnosed a papillary thyroid carcinoma (PTC) in a lymph node metastasis (LNM). Total thyroidectomy with lymphadenectomy of central and ipsilateral compartment was performed. Histopathology identified a 2 mm follicular variant of PTC and LNM in 25/25 lymph nodes. The patient was treated with 150 mCi of radioactive iodine (RAI), followed by levothyroxine suppressive therapy. In 2016, a retrotracheal mass was diagnosed, suggesting local recurrence; patient was submitted to surgical excision and RAI therapy (120 mCi). Due to seizures, in 2019, a brain CT was performed that diagnosed brain metastases. The patient underwent debulking of the main lesion. Histopathology analysis confirmed a metastatic lesion with variated morphology: classical PTC and follicular pattern and hobnail and tall cell features. Molecular analysis revealed BRAFV600E in LNM at presentation and BRAFV600E and TERT promoter (TERTp) mutations in the recurrent LNM and brain metastasis. Based upon this experience we review the reported cases of subcentimetric PTC with brain metastases and discuss the molecular progression of the present case.
Learning points
-
Papillary microcarcinoma (PMCs) usually have very good prognosis with low impact on patient survival.
-
PMCs presenting in elderly patients with LNM at diagnosis may carry a guarded outcome.
-
Brain metastasis although rare indicate aggressive phenotypic features.
-
Patient risk stratification of PMCs based on histopathological analysis and genetic testing may have a significant impact on prognosis providing therapeutic markers, that may predict disease progression and overall outcome.
Department of Internal Medicine, Regional Hospital, Horsens, Denmark
Search for other papers by Vivi-Nelli Mäkinen in
Google Scholar
PubMed
Search for other papers by Stine Horskær Madsen in
Google Scholar
PubMed
Department of Internal Medicine, Gødstrup Hospital, Herning,Denmark
Search for other papers by Mette Ji Riis-Vestergaard in
Google Scholar
PubMed
Search for other papers by Mette Bjerre in
Google Scholar
PubMed
Search for other papers by Steen Bønløkke Pedersen in
Google Scholar
PubMed
Search for other papers by Sylvia L Asa in
Google Scholar
PubMed
Search for other papers by Lars Rolighed in
Google Scholar
PubMed
Department of Clinical Medicine, Aarhus University, Aarhus University Hospital, Aarhus, Denmark
Search for other papers by Jens Otto Lunde Jørgensen in
Google Scholar
PubMed
Search for other papers by Marie Juul Ornstrup in
Google Scholar
PubMed
Summary
This case report describes a rare presentation of ectopic Cushing’s syndrome (CS) due to ectopic corticotropin-releasing hormone (CRH) production from a medullary thyroid carcinoma (MTC). The patient, a 69-year-old man, presented with symptoms of muscle weakness, facial plethora, and easy bruising. An inferior petrosal sinus sampling test (IPSS) demonstrated pituitary adrenocorticotrophic hormone (ACTH) secretion, but a whole-body somatostatin receptor scintigraphy (68Ga-DOTATOC PET/CT) revealed enhanced uptake in the right thyroid lobe which, in addition to a grossly elevated serum calcitonin level, was indicative of an MTC. A 18F-DOPA PET/CT scan supported the diagnosis, and histology confirmed the presence of MTC with perinodal growth and regional lymph node metastasis. On immunohistochemical analysis, the tumor cell stained positively for calcitonin and CRH but negatively for ACTH. Distinctly elevated plasma CRH levels were documented. The patient therefore underwent thyroidectomy and bilateral adrenalectomy. This case shows that CS caused by ectopic CRH secretion may masquerade as CS due to a false positive IPSS test. It also highlights the importance of considering rare causes of CS when diagnostic test results are ambiguous.
Learning points
-
Medullary thyroid carcinoma may secrete CRH and cause ectopic CS.
-
Ectopic CRH secretion entails a rare pitfall of inferior petrosal sinus sampling yielding a false positive test.
-
Plasma CRH measurements can be useful in selected cases.
Search for other papers by Emmanuel Ssemmondo in
Google Scholar
PubMed
Search for other papers by Mohamed Akasha Idris in
Google Scholar
PubMed
Search for other papers by Damian Mawer in
Google Scholar
PubMed
Search for other papers by Nicholas Easom in
Google Scholar
PubMed
Search for other papers by Jonathan Thow in
Google Scholar
PubMed
Summary
Mpox (MPX) formerly known as monkeypox was declared a public health emergency of international concern, following an outbreak that commenced in May 2022. We report a case of subacute thyroiditis following MPX infection. To our knowledge, it is the first documented incidence of this complication in humans. A 51-year-old male, with a well-controlled human immunodeficiency virus (HIV) infection on antiretroviral therapy, was reviewed 3 weeks after a positive test for MPX. The acute skin lesions and initial systemic symptoms had resolved, but he described significant neck discomfort, fatigue, weight loss and night sweats. Blood tests showed a raised C-reactive protein, free T4 and suppressed thyroid-stimulating hormone. His thyroid antibodies were negative. He was treated initially with carbimazole and propranolol, pending exclusion of any other intercurrent infection. A chest radiograph was normal; blood cultures and a combined nose and throat swab for respiratory virus PCR testing were negative. Following this, he commenced a 2-week course of prednisolone; his symptoms resolved completely within 24 h of starting. He subsequently developed hypothyroidism, which was treated with levothyroxine. The clinical features, abnormal thyroid function, raised CRP and negative thyroid antibodies 3 weeks post-MPX positive test was consistent with viral subacute thyroiditis. This case demonstrates that, as described following other viral infections, MPX can cause subacute thyroiditis, which follows a similar course to the classic form of subacute thyroiditis. Clinicians should be aware of this potential endocrine complication when attending to patients with MPX.
Learning points
-
Subacute thyroiditis can present following mpox virus infection.
-
Its course is similar to the classic form of subacute thyroiditis and steroids are effective.
-
It is important to exclude other concurrent infections prior to starting steroids, especially for patients who are immunosuppressed or in other high-risk groups.
