Parathyroid carcinoma: Single centre experience.

OBJECTIVE: Parathyroid Carcinoma is a rare malignant neoplasm, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single centre regarding the management and outcome of patients with parathyroid carcinomas and revise relevant literature. DESIGN: Retrospective review of all patients with parathyroid carcinoma evaluated at a tertiary oncologic centre from 1991 until 2021. RESULTS: Seventeen patients were identified (10 males), with a mean age at diagnosis of 53 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 15), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and mean PTH of 1173 pg/ml (276-2500). Hyperparathyroidism-mediated organ damage was observed in most patients (n = 16), with predominant renal (n = 12) and skeletal (n = 9) complications. En bloc surgical resection was performed in nine patients. Three patients underwent adjuvant radiotherapy. Recurrence was observed in 8 cases (47.1%) after a median of 24 months following surgery and no independent predictors of recurrence were identified. The overall survival and disease specific survival at 5-year was 88% and 94%, respectively. CDC73 mutations were present in 38.5% of analysed patients and one patient was diagnosed with MEN1. CONCLUSION: Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Therefore, preoperatively high index of suspicion is paramount to optimize patient care. This is, to our knowledge, the largest Portuguese cohort published so far.

Clinical outcomes of a conservative approach in cervical lymph node metastases of thyroid cancer.

CONTEXT: Lymph node metastases (LNM) can be present in 35% of patients with differentiated thyroid cancer (DTC), and the management of persistent/recurrent nodal disease has been controversial. Watchful waiting may be a reasonable approach in selected patients, but uncertainty about clinical outcomes remains a concern. OBJECTIVE: To investigate the outcomes of patients with DTC with recurrent/persistent confirmed LNM under surveillance. METHODS: Patients with LNM from DTC were selected from databases of needle washout thyroglobulin measurements and fine-needle aspiration biopsies performed in our institution. Patients with confirmed metastases, in whom active surveillance was initially proposed, were selected. Main clinical outcomes were analysed. RESULTS: We found 89 patients with LNM under surveillance. Classic papillary was the most frequent variant (44%). During a median follow-up of 3 (0.5-17.2) years, different treatments were needed in 35 (39.3%) patients: radioactive iodine (RAI) in 23 (25.8%), surgery in 9 (10.1%) and radiotherapy (RT) in 3 (3.4%). From those submitted initially to RAI, progression of disease was observed in 8 patients, 4 requiring other treatment modalities: surgery (n = 2), RT (n = 1) and RAI (n = 1). The remaining 54 (60.7%) patients maintained surveillance. In this group, progression of disease was observed in 26 (48.1%), due to increase in the number and/or volume of metastases, but further treatments were not required. CONCLUSION: In a group of patients with cervical LNM under active surveillance, only 16.9% (n = 15) required invasive intervention (surgery or RT).

Surveillance of succinate dehydrogenase gene mutation carriers: Insights from a nationwide cohort.

OBJECTIVE: Mutations in the genes coding for succinate dehydrogenase (SDHx) are the most frequent germline alterations in pheochromocytomas and paragangliomas. Evidence for the advantages associated with presymptomatic screening for SDHx mutation carriers is scarce. This study describes a nationwide cohort of these mutation carriers and aims to compare patients with clinical manifestations of the disease and those diagnosed through genetic screening. DESIGN: Cross-sectional study. PATIENTS: SDHx mutation carriers (n = 118) followed through the Portuguese Oncology referral centres: 41 probands and 77 nonprobands. MEASUREMENTS: All participants were subjected to biochemical and body imaging examinations for a complete assessment of the extent and spread of disease. Clinical data obtained this way were further analysed. RESULTS: The mean age of this cohort was 44.5 ± 17.4 years, and more than half carried the same founder SDHB mutation. About 50.8% of the mutation carriers developed pheochromocytomas or paragangliomas. Compared to patients diagnosed through genetic screening, those diagnosed clinically were characterized by larger tumours (P < .001), more frequent metastases (P = .024), were more frequently subjected to surgery (P = .011) and radiotherapy (P = .013), and had worse outcomes, such as macroscopic positive margins (P = .034). Persistent and/or unresectable disease and disease-related mortality were also more frequent in symptomatic patients compared to those diagnosed through genetic screening (P = .014). CONCLUSIONS: In this nationwide cohort study, a large proportion of mutation carriers were found to develop SDHx-related neoplasia. Genetic testing and subsequent follow-up resulted in the diagnosis of smaller and nonmetastatic tumours, fewer treatment procedures, fewer complications and greater number of disease-free patients.

Sexual Dysfunction and Satisfaction in Kidney Transplant Patients.

INTRODUCTION: 10% of the world's population suffers from chronic kidney disease. Kidney transplants provide an improvement in the quality of life of those patients. Sexual dysfunction is common after kidney transplantation, and its etiology is presumed to be multifactorial. It has a negative impact on sexual satisfaction and health-related quality-of-life. The integration of a new organ into the body can imply an adjustment of body image, which may eventually have a negative influence on intimacy and sexual behaviors. AIM: To evaluate male sexual function, sexual satisfaction, and body image satisfaction among a convenience sample of patients who have had a kidney transplant. METHODS: This is a cross-sectional study that included 460 patients, from a single healthcare center, who had undergone a kidney transplant procedure >4 weeks ago. A total of 112 respondents (mean = 55.5 years, SD = 11.4) answered the questionnaires properly. MAIN OUTCOME MEASURES: All recruited patients answered a self-reported sociodemographic questionnaire, in addition to the International Index of Erectile function, the New Scale of Sexual Satisfaction, the Brief Symptom Inventory, and the Body Image Scale. RESULTS: A correlation was found between sexual function and sexual satisfaction (r = 0.598, P < .001, n = 112), as well as between body image satisfaction and sexual function (r = -0.193, P = .042, n = 112). The length of time after a kidney transplant (≤ or >36 months) was not associated with a difference in sexual functioning or sexual satisfaction. CLINICAL IMPLICATIONS: This study showed the obvious implications of sexual function on sexual satisfaction, which should alert healthcare professionals to the importance of identifying and managing sexual dysfunction in patients with chronic kidney disease, to optimize their global and sexual health satisfaction. STRENGTH & LIMITATIONS: This study identified a high prevalence of sexual dysfunction among kidney transplant recipients. This should reinforce the need for the medical community to evaluate the quality-of-life domains of patients with chronic disease. There is still a lack of information concerning any longitudinal evaluation of kidney transplant patients' sexual function and the effects that this surgery has on sexuality. CONCLUSIONS: This study corroborated the severe effects that kidney transplant patients often report regarding their sexuality. Among the patients who participated in the study, sexual function proved to be relevant in relation to sexual satisfaction. Mota RL, Fonseca R, Santos JC, et al. Sexual Dysfunction and Satisfaction in Kidney Transplant Patients. J Sex Med 2019;16:1018-1028.

The management of bilateral cryptorchidism in the adult man: report of two cases.

OBJECTIVE: Undescended testis or cryptorchidism is a pathology usually presenting in the newborn or during childhood, rarely diagnosed in the adult man. This article pretends to perform a review of its management in the adulthood. METHODS: We present two cases of man with bilateral congenital cryptorchidism diagnosed in the adult. We made a review of the management of this condition in the adult male, based in a research performed in PubMed database. CONCLUSIONS: With the use of laparoscopy in the management of men with cryptorchidism, the diagnostic and therapeutic approach in this pathology doesn't differ from that used in childhood. Surgical management is based in the localization of the testis in physical exploration, the risk of testicular cancer and the viability of the gonad in its exploration. Hormonal replacement therapy and fertility preservation techniques should be offered in selected cases to optimize patient health and desires.

Adrenal findings in FDG-PET: analysis of a cohort of 1021 patients from a cancer center.

PURPOSE: The use of FDG-PET for cancer staging has led to the increasing incidence of adrenal lesions, which are usually a clinical challenge. We aimed to characterize the adrenal lesions found in FDG-PET of patients followed in a cancer center. METHODS: Retrospective analysis was conducted of all FDG-PET studies performed in our center in the last 10 years. Exams reporting adrenal lesions in the CT component and/or anomalous adrenal FDG uptake were selected. Cases were characterized by the clinical, laboratory, imaging, and pathological findings. RESULTS: We identified 27,427 FDG-PET studies. Of those, 7.6% reported adrenal findings. We included 1364 exams corresponding to 1021 patients. Only 15.6% of the patients were referred to the Endocrinology Department and 38% of the lesions were not studied. In 38.9% of the studied patients, malignant lesions were present, including metastases in 37.5%, carcinoma in 1.2%, and other malignant tumors in 0.4%. The median SUVmax of malignant lesions was significantly higher than the SUVmax of the benign findings (p < 0.05). We also observed a higher median SUVmax in adrenal metastases than in adenomas (p < 0.05). There was a tendency for higher SUVmax of adrenal carcinomas when compared with other malignant lesions (p = 0.066). The median SUVmax was not different between pheochromocytomas and other tumors (p > 0.05). CONCLUSION: Occult adrenal lesions discovered during FDG-PET/CT are common in the cancer context and are frequently benign. SUVmax may be a useful tool in the workup of adrenal lesions but with several important caveats.

Metastatic follicular thyroid cancer with a longstanding responsiveness to gemcitabine plus oxaliplatin.

Background: Treatment of advanced follicular thyroid carcinoma (FTC) is based primarily on indirect evidence obtained with multikinase inhibitors (MKI) in clinical trials in which papillary carcinomas represent the vast majority of cases. However, it should be noted that MKI have a non-negligible toxicity that may decrease the patient's quality of life. Conventional chemotherapy with GEMOX (gemcitabine plus oxaliplatin) is an off-label therapy, which seems to have some effectiveness in advanced differentiated thyroid carcinomas, with a good safety profile, although further studies are needed. Case report: We report a case of a metastatic FTC, resistant to several lines of therapy. However, with a durable response to GEMOX, the overall survival of our patient appears to have been extended significantly due to this chemotherapy. Conclusion: GEMOX may have a role in patients with thyroid cancer unresponsive to MKI.

[Proposal for a Guideline of Risk Reduction and Sensitivity Optimization in Imaging Tests for People with Diabetes]. / Proposta de Protocolo para Redução dos Riscos e Otimização da Sensibilidade nos Exames de Imagem em Pessoas com Diabetes.

Diabetes is a very common chronic disease in the Portuguese population, with an estimated prevalence of 13.6% in the adults. Doubts often arise regarding the best preparation and the risks associated with doing imaging tests in these patients. In this article we intend to review the main precautions in imaging tests in people with diabetes and to suggest a guideline to reduce the risks and optimize the sensitivity of these tests in this population. The main topics addressed in this article are the need to suspend metformin after the administration of endovascular iodinated contrast due to the risk of lactic acidosis, the precautions in insulin-treated patients or those taking medicines with a higher risk of hypoglycemia when performing imaging tests that require fasting, and the influence of hyperglycemia and of anti-diabetic therapy on the sensitivity of PET-FDG. With this review and the presentation of a guideline, we intend to demystify and simplify the management of individuals with diabetes who are undergoing imaging tests.

A diabetes é uma doença crónica muito frequente na população portuguesa, sendo a sua prevalência estimada de 13,6% nos adultos. A melhor preparação e os riscos associados à realização de exames de imagem em pessoas com diabetes são frequentemente objeto de dúvidas. Neste artigo, pretendemos rever as principais precauções e sugerir um protocolo de atuação, de forma a reduzir os riscos e otimizar a sensibilidade destes exames nesta população. Revemos também a necessidade de suspensão de metformina após a administração de contraste iodado endovascular, pelo risco de acidose láctica, as precauções em pessoas com diabetes insulinotratadas ou sob fármacos que apresentam maior risco de hipoglicemia na realização de exames de imagem que obriguem a jejum, e a influência da hiperglicemia e da terapêutica anti-diabética na sensibilidade da PET-FDG. Com a revisão deste tema e apresentação de um protocolo de atuação pretendemos desmistificar a orientação dos indivíduos com diabetes que vão ser submetidos a exames de imagem, tornando mais simples a sua gestão.

Malignant Struma Ovarii with Concurrent Thyroid Cancer: Outcomes during and after Pregnancy.

INTRODUCTION: Struma ovarii (SO) is a rare ovarian teratoma characterized by the presence of thyroid tissue in more than 50% of the tumor. Malignant transformation is rare and the most common associated malignancy is papillary thyroid carcinoma (PTC). Pregnancy may represent a stimulus to differentiated thyroid cancer (DTC) growth in patients with known structural or biochemical evidence of disease, but data about malignant SO evolution during pregnancy are rare. We present the first reported case of a pregnant patient with malignant SO and biochemical evidence of disease. CASE PRESENTATION: A previously healthy 35-year-old female diagnosed with a suspicious left pelvic mass on routine ultrasound was submitted to laparoscopic oophorectomy which revealed a malignant SO with areas of PTC. A 15-mm thyroid nodule (Bethesda V in the fine-needle aspiration cytology) was detected by palpation and total thyroidectomy was performed. Histology revealed a 15 mm follicular variant of PTC (T1bNxMx). Subsequently, she received 100 mCi of radioactive iodine therapy (RAIT) with the whole-body scan showing only moderate neck uptake. Her suppressed thyroglobulin (Tg) before RAI was 1.1 ng/mL. She maintained biochemical evidence of disease, with serum Tg levels of 7.6 ng/mL. She got pregnant 14 months after RAIT, and during pregnancy, Tg increased to 21.5 ng/mL. After delivery, Tg decreased to 14 ng/mL but, 6 months later, rose again and reached 31.9 ng/mL on the last follow-up visit. TSH was always suppressed during follow-up. At the time of SO diagnosis, a chest computed tomography scan showed 4 bilateral lung micronodules in the upper lobes which were nonspecific, and 9 months after diagnosis, a pelvic MRI revealed a suspicious cystic nodule located on the oophorectomy bed. These lung and pelvic nodules remained stable during follow-up. Neck ultrasonography, abdominal MRI, and fluorodeoxyglucose-positron emission tomography showed no suspicious lesions. DISCUSSION/CONCLUSION: As for DTC, pregnancy seems to represent a stimulus to malignant SO growth. This can be caused by the high levels of estrogen during pregnancy that may bind to receptors in malignant cells and/or by the high levels of hCG which is known to stimulate TSH receptors.

ADRENAL MICROCYSTIC RETICULAR SCHWANNOMA.

OBJECTIVE: Schwannomas are usually benign tumors, originating from the Schwann cell myelin sheath around the peripheral or cranial nerves. Visceral schwannomas are rare, and less than 60 cases of adrenal schwannomas have been reported. Microcystic/reticular schwannoma (MRS) is the rarest variant of schwannoma and only 2 cases have been reported in the adrenal gland. Here we describe a third case. METHODS: We describe a case of an adrenal MRS with a comprehensive literature review. RESULTS: The patient was a 69-year-old, Caucasian female with abdominal pain. An abdominal computed tomography scan revealed a solid, lobulated, 78-mm mass of the left adrenal gland. Two inconclusive adrenal biopsies were performed and then she was referred to our tertiary center for further evaluation. No clinical or laboratorial signs of endocrine dysfunction were identified. A positron emission tomography scan with fluorodeoxyglucose showed a single left adrenal hypermetabolic mass (SUVmax = 71.7), suggestive of malignancy. In this context, an open left adrenalectomy was undertaken. The histologic evaluation showed an MRS. CONCLUSION: Adrenal MRSs are extremely rare tumors. Definitive diagnosis of schwannoma can only be made by surgical excision with histopathologic and immunohistochemical evaluation of the specimen.

SDHx-related pheochromocytoma/paraganglioma - genetic, clinical, and treatment outcomes in a series of 30 patients from a single center.

PURPOSE: Germline mutations in the four genes that encode the succinate dehydrogenase complex (SDHx) are a risk factor for developing pheochromocytomas and/or paragangliomas. The precise genotype-phenotype correlations are still uncertain and the most common SDHx genetic defects in the Portuguese population are poorly described. The objectives of our study were to characterize the genetic alterations, clinical features, and treatment outcomes of a cohort of SDHx-related pheochromocytomas and/or paragangliomas patients. METHODS: Single center, retrospective analysis based on the presence of a SDHx mutation in cases diagnosed from 1986 until October 2016. RESULTS: Thirty cases were included. The mean age at diagnosis was 36.8 years (±15.4 years) and 53.3% were females. Remission was observed in 33.3% and stable disease (including partial responses) in 53.0%. SDHC and SDHD patients were prone to develop single and multiple head and neck paragangliomas, respectively. SDHB patients carried an increased risk of malignancy. Deletions in SDHB exon-1 and in SDHD exon-4 were the most common genetic findings. SDHB patients and head and neck paragangliomas had the worse prognosis, the former related to malignancy, and the latter to cranial nerve deficits, unresectable disease, and multimodality interventions. Peptide receptor radionuclide therapy and radioactive iodine MIBG therapy proved to be ineffective. Radiotherapy represented a good alternative in unresectable head and neck paragangliomas and in bone metastases. CONCLUSION: This single center study is the most complete Portuguese cohort in the literature and helps to understand the behavior of tumors based on their genotype and anatomical location.

Congenital hyperinsulinism in two siblings with ABCC8 mutation: same genotype, different phenotypes.

Congenital hyperinsulinism (CHI) is a heterogenous disease caused by insulin secretion regulatory defects, being ABCC8/KCNJ11 the most commonly affected genes. Therapeutic options include diazoxide, somatostatin analogues and surgery, which is curative in focal CHI. We report the case of two siblings (born two years apart) that presented themselves with hypoketotic hyperinsulinemic persistent hypoglycemias during neonatal period. The diagnosis of diffuse CHI due to an ABCC8 compound mutation (c.3576delG and c.742C>T) was concluded. They did not benefit from diazoxide therapy (or pancreatectomy performed in patient number 1) yet responded to somatostatin analogues. Patient number 1 developed various neurological deficits (including epilepsy), however patient number 2 experienced an entirely normal neurodevelopment. We believe this case shows how previous knowledge of the firstborn sibling's disease contributed to a better and timelier medical care in patient number 2, which could potentially explain her better neurological outcome despite their same genotype.

Primary adrenal insufficiency in adult population: a Portuguese Multicentre Study by the Adrenal Tumours Study Group.

INTRODUCTION: Primary adrenal insufficiency (PAI) is a rare but severe and potentially life-threatening condition. No previous studies have characterized Portuguese patients with PAI. AIMS: To characterize the clinical presentation, diagnostic workup, treatment and follow-up of Portuguese patients with confirmed PAI. METHODS: This multicentre retrospective study examined PAI patients in 12 Portuguese hospitals. RESULTS: We investigated 278 patients with PAI (55.8% were females), with a mean age of 33.6 ± 19.3 years at diagnosis. The most frequent presenting clinical features were asthenia (60.1%), mucocutaneous hyperpigmentation (55.0%) and weight loss (43.2%); 29.1% of the patients presented with adrenal crisis. Diagnosis was established by high plasma ACTH and low serum cortisol in most patients (43.9%). The most common aetiology of PAI was autoimmune adrenalitis (61.0%). There were 38 idiopathic cases. Autoimmune comorbidities were found in 70% of the patients, the most frequent being autoimmune thyroiditis (60.7%) and type 1 diabetes mellitus (17.3%). Seventy-nine percent were treated with hydrocortisone (mean dose 26.3 ± 8.3 mg/day) mostly in three (57.5%) or two (37.4%) daily doses. The remaining patients were treated with prednisolone (10.1%), dexamethasone (6.2%) and methylprednisolone (0.7%); 66.2% were also on fludrocortisone (median dose of 100 µg/day). Since diagnosis, 33.5% of patients were hospitalized for disease decompensation. In the last appointment, 17.2% of patients had complaints (7.6% asthenia and 6.5% depression) and 9.7% had electrolyte disturbances. CONCLUSION: This is the first multicentre Portuguese study regarding PAI. The results emphasize the need for standardization in diagnostic tests and etiological investigation and provide a framework for improving treatment.

Nodular Lymphocyte Predominant Hodgkin Lymphoma of the Thyroid.

Thyroid lymphomas are rare clinical entities that may result from either the primary intrathyroid de novo or secondary thyroid gland involvement of a lymphoma. Among these, the Hodgkin's subtype is quite uncommon, accounting for 0.6-5% of all thyroid malignancies. The authors report on a 76-year-old female presenting with a thyroid nodule that, upon surgical excision, was found to be a nodular lymphocyte predominant Hodgkin lymphoma of the thyroid. So far, thyroid involvement by this variant has never been reported. Upon reporting on this clinical case, the authors emphasize the difficulties usually found in establishing the diagnosis and in defining the best management strategy. A thorough review of the available literature is done.

Congenital hyperinsulinism in two siblings with ABCC8 mutation: same genotype, different phenotypes

SUMMARY Congenital hyperinsulinism (CHI) is a heterogenous disease caused by insulin secretion regulatory defects, being ABCC8/KCNJ11 the most commonly affected genes. Therapeutic options include diazoxide, somatostatin analogues and surgery, which is curative in focal CHI. We report the case of two siblings (born two years apart) that presented themselves with hypoketotic hyperinsulinemic persistent hypoglycemias during neonatal period. The diagnosis of diffuse CHI due to an ABCC8 compound mutation (c.3576delG and c.742C>T) was concluded. They did not benefit from diazoxide therapy (or pancreatectomy performed in patient number 1) yet responded to somatostatin analogues. Patient number 1 developed various neurological deficits (including epilepsy), however patient number 2 experienced an entirely normal neurodevelopment. We believe this case shows how previous knowledge of the firstborn sibling's disease contributed to a better and timelier medical care in patient number 2, which could potentially explain her better neurological outcome despite their same genotype.

[Low-level laser therapy in the treatment of diabetic ulcers: an evidence problem]. / Laserterapia de baixa potência no tratamento de úlceras diabéticas: um problema de evidência.

INTRODUCTION: Diabetes Mellitus is the leading cause of lower limb amputation, representing a significant economic cost for health services. The development of diabetic ulcers is a main risk factor for amputations, which have a high mortality rate at five years. The ischemia caused by macrovascular disease is a key pathophysiological factor in the development of ischemic ulcers. Existing treatments are prolonged and associated with high rates of failure and relapse, requiring the combination of multiple therapeutic modalities. Lowlevel laser therapy has been used as an adjuvant therapy for diabetic foot ulcers, since the 1960's, due to its hypothetical stimulating effects over microcirculation and tissue repair. MATERIAL AND METHODS: Identification of published scientific studies through a literature search on PubMed, The Cochrane Library and Cochrane Controlled Trials Register. DISCUSSION AND CONCLUSIONS: Existing evidence is favourable for in vitro cell models, but conflicting in animal models and human populations. There is significant methodological heterogeneity, which may be responsible for discordant results. Guidelines are proposed for future studies in this area, including the detailed characterization of ulcers and the parameters of laser treatment. Well-controlled studies, randomized and double-blind are needed. Accordingly to the primum non nocere, laser therapy can and should be used as adjunctive therapy in the treatment of diabetic foot, because it isn't invasive, has low costs and is a fast therapy without significant adverse effects.