Metastatic diffuse follicular variant papillary thyroid cancer without cervical lymph node metastasis presenting with symptoms related to hypopituitarism

ABSTRACT In this article, we present a case of diffuse follicular variant papillary thyroid carcinoma with pituitary metastasis, which is a rare cause of pituitary metastasis. The follicular variant of papillary thyroid carcinoma is an uncommon variant of papillary carcinoma. A 74-year-old male was presented with weakness, fatigue, and a decreased appetite. The patient was diagnosed with secondary adrenal and thyroid insufficiencies. Imaging revealed a pituitary mass with suprasellar extension, right cavernous sinus invasion, and optic chiasm compression. Thyroid ultrasonography revealed a nodule with a maximum size of 7.2cm in the right lobe. Cytological examination via fine-needle aspiration suggested papillary thyroid cancer. Total thyroidectomy with central and right lateral neck dissection confirmed the diagnosis of diffuse follicular variant of papillary thyroid carcinoma. Owing to visual field defects, the patient underwent transsphenoidal surgery. Histological and immunohistochemical evaluations confirmed pituitary metastasis from the papillary thyroid cancer. Radioactive iodine treatment and gamma knife radiotherapy of the pituitary gland were performed. The initiation of sorafenib treatment was deemed appropriate during the follow-up. A significant decrease in the thyroglobulin levels was observed after sorafenib treatment. Pituitary metastasis should be considered in patients diagnosed with hypopituitarism and pituitary lesions at initial evaluation. The presence of visual field defects may be an indication for neurosurgical intervention and guide both diagnosis and treatment. The management of papillary thyroid cancer and the role of treatment modalities in prognosis depend on the biological behavior of the tumor. Early diagnosis and multidisciplinary management are crucial for the treatment of these patients.

Efficacy of cabergoline add-on therapy in patients with acromegaly resistance to somatostatin analogs treatment and the review of literature

ABSTRACT Objective: It is reported that adding cabergoline to somatostatin analog (SSA) normalizes IGF-1 levels approximately in one-third of patients with acromegaly. We investigated the effect of combination therapy and potential predictors of response in patients with acromegaly who do not respond to SSA therapy alone. Subjects and methods: Fifty acromegaly patients (M/F 23/27, mean age 50.88 ± 12.34 years) were divided into two groups as the active and control groups in this connection. Before and after treatment, we not only evaluated serum GH and IGF-1 levels and tumor size but also analyzed the factors relevant to the effect of the combined therapy. Results: Adding cabergoline to SSA treatment led to IGF-1 normalization in 42% (21/50) of patients. Mean GH levels decreased from 2.64 ± 1.79 to 1.34 ± 0.99 ng/mL (p < .0001) and IGF-1 levels decreased from 432.92 ± 155.61 to 292.52 ± 126.15 ng/mL (p < .0001). GH and IGF-1 reduction in percent (%) were significantly higher in the controlled group (63% to 40%, p = 0.023 and 45% to 19%, p = 0.0001). Moreover, tumor size decrease was significantly higher in controlled group (-3.6 cm to -1.66 cm, p = 0.005). Conclusions: According to the results of our study, the addition of cabergoline to SSA normalized IGF-1 levels in a considerable amount of acromegaly patients with a moderately elevated IGF-1 level, regardless of serum PRL levels. Besides, cabergoline treatment was also influential in patients with higher IGF-1 levels despite a lower remission rate.

Two cases of subacute thyroiditis after different types of SARS-CoV-2 vaccination

SUMMARY Although the development of subacute thyroiditis (SAT) following viral infections is well-documented, the actual mechanism has not been clearly elucidated. The occurrence of SAT after vaccination has been reported in several case series and possible mechanisms such as molecular mimicry due to the exposure to viral proteins and/or abnormal reactogenicity by adjuvants have been implicated. We describe two cases who developed SAT three days after the messenger RNA vaccine against COVID-19 (Pfizer-BioNTech®) and six days after the inactivated COVID-19 vaccine (CoronaVac®). SAT diagnosis of these patients was delayed for more than two weeks. When the current cases were evaluated together with 1 Pfizer-BioNTech® and 3 CoronaVac® related cases reported previously, the patients were female aged between 30-42, except for the male patient we presented, and the complaints of the patients initiated within the first 2-7 days. While two Pfizer-BioNTech® vaccine-related cases were severely symptomatic and thyrotoxic at presentation, there were cases with mild to moderate clinical manifestations in CoronaVac® vaccine-related group. Physicians should be aware of SAT that may occur within a few days following the COVID-19 vaccination.

The contribution of ultrasonographic findings to the prognosis of subacute thyroiditis

ABSTRACT Objective Ultrasound assessment plays an important role in the diagnosis, and monitoring of subacute thyroiditis (SAT). However, the relationship between ultrasonographic findings and severity or prognosis of the disease is not known. The aim of the present study was to evaluate the relationship between bilateral and unilateral disease involvement and severity and prognosis of the disease. Subjects and methods The initial laboratory values, ultrasonographic findings and long-term outcomes of 247 SAT patients were evaluated retrospectively. Results In the ultrasonographic evaluation, bilateral involvement was detected in 154 patients, and unilateral involvement in 93 patients at the time of diagnosis. No significant difference was found between patients with bilateral or unilateral disease at the time of diagnosis in respect of the initial acute phase reactants. FT4 was significantly higher and TSH was significantly lower in the group with bilateral disease. Bilobar or unilobar disease on ultrasound at the time of diagnosis was not found to be a risk factor for permanent hypothyroidism or recurrence. The mean thyroid volume was determined to be 22.5 ± 10 cm3 at the beginning of treatment, and 11.2 ± 8 cm3 at the end of treatment. The initial thyroid volume and the thyroid volume at the end of treatment were significantly lower in patients who developed hypothyroidism. Conclusion There was no relationship between initial acute phase reactants and bilateral or unilateral involvement of the disease. FT4 levels were found to be associated with the extension of the disease. The risk of recurrence and permanent hypothyroidism are not associated with the initial ultrasonographic aspect. Arch Endocrinol Metab. 2020;64(3):306-11

Acute spontaneous suppurative thyroiditis caused by Eikenella corrodens presented with thyrotoxicosis / Tireoidite supurativa espontânea aguda causada por Eikenella corrodens acompanhada de tireotoxicose

ABSTRACT Acute suppurative thyroiditis is a very rare and life-threatening endocrine emergency. Thyrotoxicosis is a rare condition accompanying acute suppurative thyroiditis. While the majority of the cases in the literature are caused by different reasons, spontaneous development is very rare. We present a patient with acute suppurative thyroiditis who presented to our clinic with thyrotoxic findings, and we compared the case to the literature. A 31-year-old male patient was admitted to our clinic with a complaint of progressive neck pain, swelling and redness on midline neck, fever, and palpitations. On physical examination, swelling, redness and tenderness were detected on the neck region that was consistent with the thyroid location. He presented with tremor on the hands, tachycardia and agitation. Thyroid function tests were compatible with thyrotoxicosis, but there were findings supporting the presence of infection in biochemistry tests. On his radiological evaluations, a heterogeneous lesion divided with small septs was observed, with consolidation areas in the left thyroid lobe. In fine needle aspiration biopsy, 2mL of purulent fluid could be aspirated due to the presence of small, separated consolidation areas. He initiated on antibiotic therapy, propranolol, steroid and symptomatic treatment. Eikenella corrodens was detected on the culture antibiogram. Antibiotic therapy was continued for 14 days due to less symptoms and better biochemical values. After treatment, the patient had normal thyroid function, had relief of fever and redness of the neck, and was followed-up. It should be kept in mind that acute suppurative thyroiditis may develop spontaneously with the findings of thyrotoxicosis, with no risk factors.

RESUMO A tireoidite supurativa aguda é uma emergência endócrina muito rara e com risco de vida. A tireotoxicose é uma doença rara, que acompanha a tireoidite supurativa aguda. A maioria dos casos descritos na literatura tem diferentes causas, mas o desenvolvimento espontâneo é muito raro. Relatamos o caso de um paciente com tireoidite supurativa aguda, que veio a nossa clínica apresentando achados tireotóxicos, e o comparamos com a literatura. Trata-se de paciente do sexo masculino, 31 anos, que foi internado em nossa clínica com queixa de dor progressiva, edema e vermelhidão na linha média do pescoço, febre e palpitações. Ao exame físico, foram observados edema, vermelhidão e sensibilidade à dor na região do pescoço, consistente com a localização da tireoide. Apresentava tremor de mãos, taquicardia e agitação. Embora os exames de função tireoidiana fossem compatíveis com tireotoxicose, houve achados que sustentavam a presença de infecção nos exames bioquímicos. Nas avaliações radiológicas, observou-se lesão heterogênea dividida por pequenos septos, com áreas de consolidação no lobo tireoidiano esquerdo. Na biópsia por aspiração por agulha fina, foi possível aspirar apenas 2mL de líquido purulento, devido à presença de pequenas áreas de consolidação separadas umas das outras. Iniciaram-se antibioticoterapia, administração de propranolol e esteroides, além de tratamento sintomático. Eikenella corrodens cresceu na cultura do antibiograma. A antibioticoterapia foi estendida por 14 dias devido à melhora nos sintomas e dos valores bioquímicos. Após o tratamento, o paciente se apresentava eutireoideo, com melhora na febre e na vermelhidão no pescoço, sendo então acompanhado. Deve-se ter em mente que a tireoidite supurativa aguda pode se desenvolver espontaneamente com achados de tireotoxicose, sem nenhum fator de risco.

Is fibroblast growth factor 23 a new cardiovascular risk marker in gestational diabetes?

ABSTRACT Objective This study was designed to compare the serum levels of fibroblast growth factor 23 (FGF23) among patients with gestational diabetes mellitus (GDM) and healthy pregnant women, and to evaluate the association between hormonal and metabolic parameters. Subjects and methods A total of 82 pregnant women were consecutively enrolled in the study. Of these, 46 were diagnosed as having GDM; the remaining 36 healthy pregnant women served as controls in a cross-sectional study design. The womens' ages ranged from 22 to 38 years and gestational ages, from 24 to 28 weeks. Serum samples were analyzed for FGF23 levels using an enzyme-linked immunosorbent assay. Results Serum FGF23 levels were increased in patients with GDM compared with controls (median, 65.3 for patients with GDM vs. 36.6 ng/mL for healthy controls; p = 0.019). Mean fasting glucose (105.6 ± 7.4 vs. 70.2 ± 7.2 mg/dL, p < 0.001), HbA1c (5.6 ± 0.5 vs. 4.9 ± 0.5%, p < 0.001), insulin (median, 11.1 vs. 8.7 µIU/mL, p = 0.006) and HOMA-IR (3.0 (1.8) vs 1.4 (0.6), p < 0.001) levels were significantly higher in patients with GDM than in controls. Serum FGF23 level was positively correlated with body mass index (r2 = 0.346, p < 0.05), FPG (r2 = 0.264, p < 0.05), insulin (r2 = 0.388, p < 0.05), HOMA-IR (r2 = 0.384, p < 0.05). Conclusion Serum FGF23 levels were higher in women with GDM compared with controls. The present findings suggest that FGF23 could be a useful marker of cardiovascular disease in GDM.

Serum ghrelin levels in papillary thyroid carcinoma

ABSTRACT Objective Ghrelin plays a role in several processes of cancer progression, and numerous cancer types express ghrelin and its receptor. We aimed to investigate serum levels of ghrelin in patients with papillary thyroid carcinoma (PTC) and its association with the prognostic factors in PTC. Materials and methods We enrolled 54 patients with thyroid cancer (7 male, 47 female) and 24 healthy controls (6 male, 18 female) in the study. We compared demographic, anthropometric, and biochemical data, and serum ghrelin levels between the groups. Serum ghrelin levels were measured using as enzyme-linked immunosorbent assay. Results Ghrelin levels were similar between the groups, but plasma ghrelin levels were significantly higher in tumors larger than 1 cm diameter compared with papillary microcarcinomas. Serum ghrelin levels also correlated with tumor size (r = 0.499; p < 0.001). Body mass index, thyroid-stimulating hormone, and HOMA-IR levels were similar between the groups. There were no statistically significant differences regarding average age and other prognostic parameters including lymph node invasion, capsule invasion, multifocality and surgical border invasion between patients with microcarcinoma and tumors larger than 1 cm. Conclusion In our study, no significant difference in serum ghrelin levels was determined between patients with papillary thyroid cancer and healthy controls however, serum ghrelin levels were higher in tumors larger than 1 cm compared to in those with thyroid papillary microcarcinoma.

A rare case of ectopic ACTH syndrome originating from malignant renal paraganglioma

SUMMARY Ectopic adrenocorticotropic hormone (ACTH) syndrome is characterized by hypercortisolism due to the hypersecretion of a non-pituitary ACTH-secreting tumor leading to Cushing's syndrome. Only a few cases have been reported previously as causing ectopic ACTH related to paraganglioma. Herein, we present a case of Cushing's syndrome, in who was proved to be attributable to an ACTH-secreting renal malignant paraganglioma. A 40-year-old woman presented with a five-month history of newly diagnosed hypertension and diabetes, weakness, hyperpigmentation, oligomenorrhea, hirsutism, and acneiform lesions. She showed cushingoid features, including moon face, facial hirsutism, facial and truncal acne, hyperpigmentation, and severe muscle weakness of the limbs. She did not have other findings such as striae, supraclavicular fat accumulation, and buffalo hump. Laboratory examination showed the presence of hypopotasemia, hyperglycemia, hyperthyroidism, and leukocytosis. The serum levels of ACTH, cortisol, and urine-free cortisol were markedly elevated. Results of an overnight 2-mg dexamethasone suppression test included a basal serum cortisol of 61.1 mcg/dL (normal range: 4.6-22.8 mcg/dL) and a cortisol value of 46.1 mcg/dL after dexamethasone administration. There was no suppression found after 2-day 8-mg dexamethasone administration. Magnetic resonance imaging (MRI) of the pituitary gland indicated two microadenomas. An abdominal MRI scan revealed horseshoe kidney, bilateral adrenal hyperplasia, and masses with dimensions of 35 x 31 mm in the left kidney. Inferior petrosal sinus sampling showed no evidence of a central-to-peripheral gradient of ACTH. A positron emission tomography/computed tomography scan showed intense increased activity in the lower pole of the left kidney. Left adrenalectomy and left partial nephrectomy were performed. The resected tumor was diagnosed as the ACTH-secreting paraganglioma in the pathological examination, which was confirmed by immunohistochemical studies with chromogranin A, synaptophysin, and ACTH. Only a few cases of paragangliomas as a cause of ectopic ACTH syndrome have been reported. To our knowledge, this is the first case of renal paraganglioma resulting in Cushing's syndrome due to ectopic ACTH hypersecretion.

Circulating E-selectin levels and insulin resistance are associated with early stages of atherosclerosis in nonfunctional adrenal incidentaloma

Objective To evaluate circulating E-selectin levels in patients with nonfunctional adrenal incidentaloma (NFA) in relation to insulin resistance and early atherosclerosis.Subjects and methods A total of 40 patients with NFA (mean [SD] age: 55.6 [10.7] years; 70% were females) and 35 controls (mean [SD] age: 51.5 [8.1] years; 71.4% were females) selected from age-, gender- and body mass index (BMI)- matched healthy subjects were enrolled. Serum hsCRP, lipid profile, insulin levels and the homeostasis model assessment of insulin resistance (HOMA-IR) were evaluated. High-resolution B-mode ultrasonography was performed. Serum levels of E-selectin were evaluated by enzyme-linked immunosorbent assay.Results Patients with NFA had significantly higher values for E-selectin (14.9 (4.8) vs. 12.2 (4.1) ng/mL, p < 0.01) and CIMT (0.6 (0.1) vs. 0.5 (0.1) mm, p < 0.05) than controls. Serum E-selectin levels showed a statistically significant association with hsCRP (r = 0.751, p < 0.001), HOMA-IR (r = 0.575, p < 0.001) and CIMT (r = 0.762, p < 0.001). CIMT (Carotid intima media thickness) was increased in patients with NFA patients with NFA were more insulin resistant than controls and statistically significant relationship was found between size of tumor and HOMA-IR (r = 0.361, p < 0.001).Conclusion In conclusion, based on significantly higher values for E-selectin, CIMT and HOMA-IR in patients with NFA than controls along with significant correlation of E-selectin levels to CIMT, HOMA-IR and hs-CRP, our findings seems to indicate an increased risk of early atherosclerosis and impaired endothelial function in NFA patients, particularly in case of insulin resistance.

Thyroid hormone resistance in two patients with papillary thyroid microcarcinoma and their BRAFV600E mutation status

Resistance to thyroid hormone (RTH) is a rare autosomal dominant hereditary disorder. Here in, we report two patients with RTH in whom differentiated thyroid cancer was diagnosed. Two patients were admitted to our clinic and their laboratory results were elevated thyroid hormone levels with unsuppressed TSH. We considered this situation thyroid hormone resistance in the light of laboratory and clinical datas. Thyroid nodule was palpated on physical examination. Thyroid ultrasonography showed multiple nodules in both lobes. Total thyroidectomy was performed. The pathological findings were consistent with papillary thyroid microcarcinoma. BRAFV600E mutation analysis results were negative. RTH is very rare and might be overlooked. There is no consensus on how to overcome the persistently high TSH in patients with RTH and differentiated thyroid cancer (DTC). Further studies are needed to explain the relationship between RTH and DTC which might be helpful for the treatment of these patients.

Transformation of nonfunctioning pancreatic tumor into malignant insulinoma after 3 years: an uncommon clinical course of insulinoma

A 62-year-old man admitted to our outpatient clinic with two months of recurrent life threatening hypoglycemia episodes. He was diagnosed as malignant insulinoma with multiple metastases of liver and peripancreatic lymph nodes. Liver biopsy specimen was demonstrated grade 2 neuroendocrine tumor compatible with clinical and radiological results. He was followed under the treatment of continuous intravenous glucose infusion during the diagnostic procedures. He had a pancreatic lesion history measured 20 x 12 mm in diameter via the abdominal tomography examination approximately two years before the diagnosis. Unusual course of this case suggests the transformation of nonfunctioning pancreatic neuroendocrine tumor into functional insulin secreting tumor with metastases. The patient was found inoperable and started on chemotherapy. Arch Endocrinol Metab. 2015;59(3):270-2.

Papillary thyroid cancer case masked by subacute thyroiditis / Caso de carcinoma papilar de tiroide mascarado por tireoidite subaguda

Subacute thyroiditis (SAT) association with thyroid carcinoma has been rarely reported in the literature. We present a patient with SAT and papillary thyroid cancer that was suspected by ultrasonographic evaluation (US) following SAT treatment. A fifty-four-year old female patient referred to our department due to tachycardia, jitteriness and pain in cervical region for the past one month. SAT diagnosis was established by physical examination, laboratory and ultrasonographic findings. After treatment, control thyroid US revealed regression of the hypoechogenic regions seen in both lobes, and a previously unreported hypoechogenic lesion with microcalcification focus that had irregular borders and was not clearly separated from the surrounding parenchyma located in the posterior aspect of the lobe (Elasto score: 4, Strain index: 7.08). Fine needle aspiration biopsy was taken from this nodule; cytology was assessed to be compatible with papillary thyroid carcinoma. Postsurgical pathology evaluation showed a papillary microcarcinoma. SAT may produce ultrasound changes that obscure the coexistence of papillary carcinoma. We recommend that patients with SAT have ultrasonography after they recover. Hypoechogenic regions bigger than 1 cm that are present in the follow-up post-therapy US should be assessed by biopsy.

A associação da tireoidite subaguda (TSA) com o carcinoma de tiroide foi raramente relatada na literatura. Apresentamos uma paciente com TSA e tumor papilar de tiroide suspeito na ultrassonografia (US) após o tratamento para a TSA. Uma mulher de 54 anos de idade foi encaminhada ao nosso departamento com taquicardia, agitação e dor na região cervical, com duração de 1 mês. O diagnóstico de TSA foi estabelecido pelo exame físico, e pelos achados laboratoriais e ultrassonográficos. Depois do tratamento, o US para controle da tiroide mostrou regressão das regiões hipoecoicas vistas em ambos os lobos e uma lesão hipoecoica anteriormente não observada com focos de microcalcificação, bordas irregulares, não claramente separada do parênquima circundante e localizada na região posterior do lobo. (Escore elástico: 4, índice de deformação: 7,08). Foi feita uma biópsia do nódulo por meio de aspiração por agulha fina. A citologia mostrou-se compatível com um carcinoma papilar de tiroide. A avaliação pós-cirúrgica mostrou um microcarcinoma papilar. A TSA pode produzir alterações ultrassonográficas que obscurecem a coexistência de carcinoma papilar. Recomendamos que pacientes com TSA passem por exame ultrassonográfico após a recuperação. Regiões hipoecoicas maiores que 1 cm encontradas no US para acompanhamento pós-tratamento devem ser avaliadas por biópsia.

Nonadenomatous nonencapsulated thymic parathyroid tissue concomitant with primary hyperparathyroidism due to ectopic parathyroid adenoma / Tecido tímico paratireoidiano não edematoso e não encapsulado concomitante com hiperparatireoidismo devido a adenoma paratireoidiano ectópico

Primary hyperparathyroidism due to ectopic parathyroid adenoma is not infrequent. Primary hyperparathyroidism caused by unusual thymic nonadenomatous nonencapsulated parathyroid tissue has been reported before. Both can cause unsuccessful neck explorations. Here we presented for the first time a patient with hyperparathyroidism due to ectopic parathyroid adenoma concomitant to the presence of thymic nonadenomatous nonencapsulated parathyroid tissue.

O hiperparatireodismo primário devido a adenoma ectópico paratireoidiano não é raro. O hiperparatireodismo primário causado por tecido tímico paratireoidiano não edematoso e não encapsulado incomum já foi relatado anteriormente. Ambos podem levar à exploração cervical malsucedida. Apresentamos aqui, pela primeira vez, uma paciente com hiperparatireoidismo decorrente de um adenoma paratireoidiano concomitante com a presença de tecido tímico paratireoidiano não edematoso e não encapsulado.