Thyroid cancer and pregnancy: a systematic ten-year-review.

Background: Thyroid cancer is the second most common malignancy during pregnancy, especially the well-differentiated thyroid cancer (well-DTC). Therefore, complex medical and social dilemmas arise, dealing with which requires deep knowledge of the nature and characteristics of the disease and pregnancy as a whole. The purpose of this review is to present the diagnostic and therapeutic strategies of thyroid cancer during pregnancy and the postpartum period. Methods: Extended review of the literature [2011-2023] was performed. Two hundred ninety-six articles were found, from which 225 were excluded due to irrelevant subjects. Seventy-one articles were assessed for eligibility, from which 33 articles were cohort studies and case reports and were included in the review. Results: From the 33 included studies, 18 were retrospective cohort studies, 1 was cohort study, 2 were case control studies, 1 was meta-analysis and 11 were case reports. The primary endpoints of these studies refer to the progression and recurrence of DTC during pregnancy, the prevalence of thyroid cancer in pregnancy and the most appropriate time for surgical intervention. Conclusions: The majority of the studies agree that well-differentiated tumors with mild clinical and imaging characteristics do not require immediate surgical treatment, but mere monitoring. Surgery can be delayed after childbirth. In contrast, tumors with aggressive behavior as well as non-differentiated ones, require immediate surgery because delay under these circumstances can dramatically reduce survival rates. Finally, a history of thyroid cancer does not seem to affect future deliveries, on condition that no residual disease exists at the onset of pregnancy.

Mönckeberg sclerosis in patients with thyroid papillary carcinoma.

Background: Mönckeberg sclerosis is a form of calcification of the tunica media of small and medium size arteries. It occurs more often in the peripheral arteries of the lower limbs and it has been associated with diabetes and renal disease. Although there are a few reports of Mönckeberg sclerosis in thyroid vessels, there are no data regarding its significance in thyroid disease. Objective: The aim was to investigate the possible prognostic value of Mönckeberg sclerosis in thyroid vessels of patients with diagnosed thyroid cancer. Methods: We retrospectively studied patients with papillary thyroid cancer treated at the Theagenio Hospital of Thessaloniki from 2005 to 2021. The patients were divided into two groups based on the presence, or absence, of histopathological findings of Mönckeberg sclerosis in the thyroid vessels along with papillary thyroid cancer. Patient characteristics, histopathological details, personal history of thyroid disease, and metabolic parameters were compared between the two groups. Results: Thirty-three patients with papillary thyroid carcinoma and Mönckeberg sclerosis were identified and matched to 33 controls with papillary thyroid cancer, without evidence of Mönckeberg sclerosis. The metabolic profile of patients with Mönckeberg sclerosis was not significantly different from those who did not have Mönckeberg sclerosis. Moreover, the comparison between the two groups did not reveal any remarkable differences in terms of the aggressiveness of the disease. Conclusion: The presence of Mönckeberg sclerosis does not seem to impact on histological characteristics of patients with papillary thyroid cancer.

Diagnostic Accuracy of Ultrasound and Fine-Needle Aspiration Cytology in Thyroid Malignancy.

Introduction: Thyroid nodule incidence is increasing due to the widespread application of ultrasonography. Fine-needle aspiration cytology is widely applied for the detection of malignancies. The aim of this study was to evaluate the predictive value of ultrasonography in thyroid cancer. Methods: This retrospective study included patients that underwent total thyroidectomy for benign thyroid disease or well-differentiated thyroid carcinoma from January 2017 to December 2022. The study population was divided into groups: the well-differentiated thyroid cancer group and the control group with benign histopathological reports. Results: In total, 192 patients were enrolled in our study; 159 patients were included in the well-differentiated thyroid cancer group and 33 patients in the control group. Statistical analysis demonstrated that ultrasonographic findings such as microcalcifications (90.4%), hypoechogenicity (89.3%), irregular margins (92.2%) and taller-than-wide shape (90.5%) were correlated to malignancy (p < 0.001). Uni- and multivariate analysis revealed that both US score (OR: 2.177; p < 0.001) and Bethesda System (OR: 1.875; p = 0.002) could predict malignancies. In terms of diagnostic accuracy, the US score displayed higher sensitivity (64.2% vs. 33.3%) and better negative predictive value (34.5% vs. 24.4%) than the Bethesda score, while both scoring systems displayed comparable specificities (90.9% vs. 100%) and positive predictive values (97.1% vs. 100%). Discussion: The malignant potential of thyroid nodules is a crucial subject, leading the decision for surgery. Ultrasonography and fine-needle aspiration cytology are pivotal examinations in the diagnostic process, with ultrasonography demonstrating better negative predictive value.

A Rare Manifestation of Secondary Hyperparathyroidism Due to Brown Tumors: A Case Report.

Purpose: Brown tumors, also known as cystic fibrosa, are rare, benign, osteolytic, fibrotic lesions of the bones that occur secondary to hyperparathyroidism. They are caused by increased osteoclastic activity leading to an abnormal bone metabolism. Case Description: Here, we present the case of a 58-year-old male, who presented with painful bony lesions, initially attributed to metastatic disease. After biochemical workout, imaging and biopsy, the nature of the lesions was revealed. We discuss the differential diagnosis and clinical management of the disease. Conclusion: Patients with brown tumors should be assessed in the differential diagnosis of bony lesions and should always be tested for hyperparathyroidism. An early diagnosis is crucial for the successful treatment of such patients.

Radioiodine refractory differentiated thyroid cancer.

Differentiated thyroid cancer is composed of papillary (85%), follicular (13%) with their subtypes and anaplastic (<2%) thyroid cancer, derived from follicular dedifferentiation. In the majority of cases (85%), treatment is succeeded with thyroxine suppression and radioiodine ablation. However, there is a small percentage of patients presenting with local recurrence or metastases during follow up. In such cases, reoperation and radioiodine treatment are the treatments of choice. 10% of the aforementioned patients appear resistance to radioiodine treatment and they are considered refractory to iodide. As refractory to radioiodine is defined a patient who fulfills one of the following criteria: 1. Negative RAI Uptake 2. RAI uptake in some but not all metastases 3. Disease progression 6-12 months after Radioiodine ablation 4. Disease progression after radioiodine treatment more of than 600mCi.

Thyroid sarcoidosis: a rare entity in the differential diagnosis of thyroid cancer.

SUMMARY: We present two cases of thyroid sarcoidosis that were misdiagnosed as thyroid cancer. In the first patient, fine needle aspiration cytology (FNAc) of a suspicious thyroid nodule indicated the presence of papillary thyroid cancer, and the patient underwent thyroid surgery. However, histopathology identified a sarcoid granuloma, without any sign of malignancy. The second patient had a history of papillary microcarcinoma with suspicious lymph nodes diagnosed years after the initial diagnosis and was referred for assessment of cervical lymphadenopathy. Fine needle aspiration cytology (FNAc) of the suspicious lymph nodes erroneously indicated metastasis from thyroid cancer, and lateral modified lymph node dissection was performed, based on FNAc and ultrasonographic features. Histopathology excluded malignancy and identified non-caseating granulomas. Sarcoidosis of the thyroid may have a clinical presentation similar to well-differentiated thyroid carcinoma and, although rare, should be considered in the differential diagnosis, especially when other signs of the disease are already present. In these cases, FNAc provided a false diagnosis of papillary thyroid carcinoma and lymph node metastases that led to unnecessary surgery. LEARNING POINTS: Sarcoidosis may share clinical and ultrasonographic features with papillary thyroid carcinoma. Fine needle aspiration cytology is helpful in the diagnosis of both conditions; however, the overlapping cytological characteristics may lead to erroneous diagnosis. The present cases illustrate the importance of cytological identification of these difficult cases. Every piece of information provided by the clinician is essential to the cytologist.

Intrathyroidal parathyroid adenoma mimicking thyroid cancer.

Primary hyperparathyroidism (PHPT) is the most common cause of hypercalcemia; patients are usually asymptomatic and the cause in 80-85% of cases is a single parathyroid adenoma (PA). Parathyroid adenomas arise from clonal expansion of tumor cells and may be located either posteriorly to the thyroid lobes or in ectopic sites. The incidence of intrathyroidal PAs varies from 1% to 6% and although uncommon, they pose certain diagnostic difficulties which may complicate treatment. The identification of the adenoma requires a combination of clinical evidence, imaging information and cytological findings due to the challenging distinction between thyroid and parathyroid lesions. We present the case of a patient with a large, partially cystic intrathyroidal parathyroid adenoma which was initially identified as a malignant thyroid nodule. We discuss the caveats that present in these rare cases and the important clinical and histological features that aid in the final diagnosis. In the case of our patient the cytological similarities between thyroid malignant cells and parathyroid cells, in combination with the negative sestamibi scan, resulted in a more invasive surgery than that a single parathyroid adenoma would require. Clinicians need to be vigilant in terms of the similarities between parathyroid and thyroid cytology in order to provide optimal patient care in these rare cases.

Patients with extra-adrenal malignancies and adrenal lesions have similar rates of subclinical hypercortisolism compared with patients with true adrenal incidentalomas.

OBJECTIVE: During follow-up in cancer patients, adrenal lesions are frequently found by computer tomography imaging. In these patients, the frequency of subclinical Cushing's syndrome (SCS) has not been fully explored. The aim of the present study was to investigate the presence of SCS in cancer patients with adrenal lesions in comparison to patients with true adrenal incidentalomas. DESIGN: We studied 95 patients with adrenal lesions: 57 patients (group A, 20 males and 37 females) had a history of extra-adrenal malignancy and adrenal lesions were discovered during staging of the primary cancer, and 38 patients (group B, 6 males and 32 females) had adrenal incidentalomas. The two groups had similar BMI. All patients had unenhanced HU < 10 in computed tomography to ensure low risk of adrenal metastatic disease. Patients' morning plasma cortisol levels and ACTH were measured. An overnight 1 mg dexamethasone suppression test (ODST) was performed in all participants; in case of abnormal results, 24-h urine cortisol and the low-dose dexamethasone suppression test were additionally conducted. The cutoffs of morning cortisol values used for ODST were 1.8 and 5 µg/dl. RESULTS: When the cutoff of 1.8 µg/dl for suppressed morning cortisol was used, 42.1% of group A and 39.5% of group B had abnormal results (p = 0.95). By using the threshold of 5 µg/dl after ODST, 5.3% of group A and 13.2% of group B did not have suppressed cortisol levels with the 1 mg ODST (p = 0.18). The main factors found to influence suppressed cortisol levels after ODST in both groups were BMI and size of the adrenal lesion. CONCLUSIONS: Patients with extra-adrenal malignancies and adrenal lesions had similar rates of subclinical hypercortisolemia compared to patients with true adrenal incidentalomas.

Loss of Efficacy of Pasireotide After its Re-Administration: is There a Reason Why?

Pasireotide is a recently approved medical treatment for persistent or recurrent Cushing's disease (CD). However, an escape from the initial successful response has not yet been described. A 42-year-old female presented with several symptoms indicative of hypercortisolism. Biochemical evaluation and imaging were consistent with CD due to a pituitary adenoma. Surgical excision of the adenoma was unsuccessful and gamma-knife radiosurgery was followed. Our patient remained hypercortisolemic thus treatment with pasireotide (900 mg subcutaneously twice daily) was decided. Biochemical and clinical remission was noted shortly thereafter. Moderate adverse events led to dose reduction to 600 mg subcutaneously twice daily. The patient remained in remission for 6 months, when treatment was discontinued due to cholecystitis. One month after cholecystectomy, pasireotide was restarted with no clinical or biochemical benefit that time. Pasireotide is an effective medical treatment for CD. Nevertheless, a loss of its initial efficacy may rarely be described.

Treatment compliance and severe adverse events limit the use of tyrosine kinase inhibitors in refractory thyroid cancer.

OBJECTIVE: The aim of the present study was to assess patient compliance with tyrosine kinase inhibitor (TKI) treatment used for refractory and progressive thyroid cancer, in addition to the efficacy and serious adverse events associated with these agents. METHODS: We retrospectively analyzed data from adult patients with metastatic differentiated or medullary thyroid cancer unresponsive to conventional treatment and treated with TKIs. Patients received treatment until disease progression or onset of serious adverse events, or until they expressed an intention to stop treatment. RESULTS: Twenty-four patients received TKIs. The median duration of treatment was four (range: 1-19) cycles. The most frequent adverse events were fatigue, nausea, diarrhea, hypertension, and stomatitis, and the most severe were nasal bleeding, diarrhea, heart failure, rhabdomyolysis, renal failure, QT prolongation, neutropenia, and severe fatigue. Dose reduction was required in eight patients, while five decided to terminate TKI therapy because adverse events impaired their everyday activities. During therapy, two patients showed a partial response and three showed stable disease. The lungs were the metastatic sites favoring a response to treatment. CONCLUSION: Patient selection and meticulous pretreatment education are necessary in order to ensure adherence with TKI therapy. If adverse events appear, dose reduction or temporary treatment interruption may be offered because some adverse events resolve with continuation of treatment. In the event of serious adverse events, treatment discontinuation is necessary.

Breast Metastasis from Medullary Thyroid Carcinoma in a Male Patient: Case Report and Review of the Literature.

Medullary thyroid carcinoma (MTC) is a rare malignancy that may metastasize to liver, lungs and bones. Breast is an unusual metastatic site for MTC and only 20 female cases have been reported in the literature. We present a male patient in whom histological examination and immunohistochemistry of a breast mass were indicative of breast metastasis from MTC. A 67-year-old man with recent diagnosis of MTC and metastases to cervical and upper mediastinum lymph nodes was referred to our department for further treatment. At first evaluation, diagnostic imaging techniques showed lung and bone metastases and three months later the presence of liver metastases. Due to the extension of the disease, treatment with vandetanib was decided, but serious adverse events led to its interruption after two weeks. During follow-up, patient developed a painful swelling in the right breast. Ultrasound and mammography showed the presence of multiple masses to the right breast suspicious for malignancy. Core needle biopsy and histological examination of the specimen confirmed the presence of metastatic MTC. Palliative external beam irradiation was used to relieve local pain and, after one month, the patient died. Consequently, breast masses should be cautiously evaluated, mainly in the presence of a known primary malignancy. Histological and/or cytopathological examination are requisite diagnostic tools, while external beam irradiation and tyrosine kinase inhibitors may be used as palliative therapies in the concurrent presence of breast metastases from MTC.

Pituitary disorders in pregnancy.

The pituitary gland is significantly affected during gestation in terms of both size and function. Due to this physiologic adaptation, endocrine evaluation and interpretation of imaging is far more complex than in the non-pregnant state. Pituitary disorders are rare in pregnancy, as they are usually associated with gonadal dysfunction, thereby posing difficulties with fertility. This review will focus on pituitary adenomas (prolactinomas, GH-secreting and ACTH-secreting), their diagnostic handicaps and the recommendations for treatment. We will also discuss the two pituitary disorders encountered in pregnancy, Sheehan's syndrome and lymphocytic hypophysitis.

Acute adrenal insufficiency following arthroplasty: a case report and review of the literature.

BACKGROUND: Acute adrenal insufficiency is a potentially lethal condition rarely caused by bilateral adrenal haemorrhage due to heparin use. Most of the times, it is difficult to establish the diagnosis, as symptoms are not specific. Few cases have been reported in the literature. CASE PRESENTATION: A 52-year-old Caucasian woman presented with abdominal pain, vomiting and weakness nine days after arthroplasty and heparin use. Hyperkalemia, low cortisol and high adrenocorticotropic hormone levels were found, indicating adrenal insufficiency. Magnetic resonance imaging of the upper abdomen was compatible with preceding adrenal haemorrhage. Hydrocortisone and fludrocortisone were administered. Review of the literature revealed 36 cases of postoperative adrenal haemorrhage which are presented briefly. CONCLUSION: Postoperative acute adrenal insufficiency due to haemorrhage is a rare condition. If patients are treated based on clinical suspicion, they have good chances to survive. Hydrocortisone is given permanently in the majority of the patients.

Mixed corticomedullary adrenal carcinoma.

Truly mixed corticomedullary tumors (MCMTs) are extremely rare and present as a single tumor mass composed of an intimately admixed population of both adrenal cortical cells and pheochromocytes. The current study describes the first case of a mixed corticomedullary adrenal carcinoma. In addition, we also review the published data on MCMTs to determine their clinical features, biochemical characteristics, pathological findings, and management. In order to compose this review, a search of the international literature for MCMTs was conducted. Fifteen related articles were found. The clinical and pathological information was obtained for all reported cases. MCMTs were found almost exclusively in females. In the vast majority of patients, the symptoms were related to the tumor's hormone hypersecretion. Hypertension and diabetes were present in 80 and 40 % of cases, respectively. Cushing's syndrome was reported in eight cases (53.33 %). A final diagnosis was made in all cases after surgery based on the pathological results. As of the writing of this article, all published cases of MCMTs had benign clinical behavior, with no instances of metastasis or death due to the tumor. MCMTs are currently considered to be benign tumors. Ours is the first case of malignant MCMT reported in the literature. The potential for malignancy should therefore be considered for these tumors.

Thyroglossal duct cyst carcinomas: is there a need for thyroidectomy?

OBJECTIVE: Thyroglossal duct cyst (TGDC) carcinoma is a rare entity and its management is controversial. The aim of this retrospective study was to: (a) identify patients with TGDC carcinoma followed up in our clinic and (b) study specific characteristics of the disease and their association with thyroid carcinoma. DESIGN: Medical files of patients with TGDC carcinoma were reviewed and tumour characteristics, lymph node metastases, treatment and follow-up were evaluated. RESULTS: A total of 6 patients, 4 females and 2 males, mean age 39.3 years (median 33.5), were treated for papillary thyroid carcinoma arising in a TGDC. Carcinoma of the thyroid gland was found simultaneously in 4 of these patients, while in one patient thyroid carcinoma developed 10 years after the diagnosis of TGDC carcinoma. A variable clinical picture and presentation was recorded. The most aggressive manifestation of the disease in terms of local infiltration, local recurrence and lymph node metastases was observed in our youngest patients. CONCLUSIONS: Long-term follow-up is necessary for patients with thyroid carcinoma arising in a TGDC. In view of the frequent co-existence of thyroid cancer in these patients, we would recommend detailed thyroid evaluation and, eventually, total thyroidectomy at initial diagnosis of TGDC carcinoma.

Parathyroid involvement in thyroid cancer: an unforeseen event.

BACKGROUND: Parathyroid metastatic disease from thyroid cancer has not been studied extensively, mainly due to the need for parathyroid preservation during thyroid surgery. METHODS: We reviewed files from 1,770 patients with thyroid cancer followed up in our department and 10 patients with parathyroid metastases (0.5%) were identified. Patient and tumor characteristics were recorded. RESULTS: Six out of ten patients had metastases from papillary thyroid cancer, three from follicular thyroid cancer and one from anaplastic thyroid cancer. In nine patients parathyroid infiltration from thyroid cancer was found in direct contact with the thyroid cancer, and in one patient metastatic foci were observed not in continuity with the thyroid cancer. CONCLUSIONS: Parathyroid involvement, although infrequent, may occur in thyroid cancer independently of patient age and tumor size. The clinical significance of such event is not clear. The influence on disease outcome remains to be elucidated.

99mTc pertechnetate thyroid scan leads to serendipitous detection of metastatic thyroid cancer.

99mTc pertechnetate is considered insensitive in detecting thyroid carcinoma metastases. We report the case of a 71-year-old male patient, in whom metastasis of an unknown thyroid cancer was diagnosed incidentally on a routine 99mTc pertechnetate scan, performed for the assessment of nodular thyroid disease. Marked tracer accumulation was unexpectedly noted on the left frontal region, where a palpable, painless, soft tissue mass was present. Surgical excision of the mass revealed metastatic poorly differentiated thyroid carcinoma synchronous to soft tissue and adjacent bone.

Histological subtype is the most important determinant of survival in metastatic papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) comprises the commonest type of thyroid cancer and carries the highest rate of survival. However, when metastatic disease occurs, survival is significantly affected. METHODS: We aimed to identify prognostic histopathological and clinical factors that modify survival in metastatic PTC. All cases of metastatic PTC treated at our department in the last 20 years were reviewed and analyzed. RESULTS: Histological subtype was the most important determinant of survival, as classic PTC demonstrated clearly improved survival compared to follicular subtype of PTC and other less frequently seen histological subtypes. The instant risk of death for the other histological subtypes was 4.56 times higher than the risk for the classic papillary type. Overall, a 10-year survival of 76.6% in our patients was seen. CONCLUSIONS: Patients with aggressive variants of PTC are more at risk for the development of metastatic disease. In these patients, established treatment modalities (surgery, radioiodine therapy) should be offered promptly, as well as close follow-up.

The hypothalamic-pituitary-adrenal axis in women with differentiated thyroid cancer.

INTRODUCTION: We studied the function of hypothalamic-pituitary-adrenal (HPA) axis in females with differentiated thyroid cancer (DTC) and its sequelae on metabolism and cardiovascular risk. METHODS AND RESULTS: Sixteen women were investigated with (1) morning, evening, and midnight cortisol and adrenocortophic hormone, (2) cortisol after overnight 1 mg dexamethasone suppression test, (3) cortisol after corticotropin releasing hormone test, (4) oral glucose tolerance test with glucose and insulin estimations, and (5) ultrasound for carotid intima media thickness. A matched control group underwent similar investigations. None of the parameters was significantly different between patients and controls. CONCLUSION: Females with DTC have normal HPA-axis function and similar insulin sensitivity and cardiovascular risk compared to controls.