A Perspective on the Current Medical Approach of Advanced Medullary Thyroid Carcinoma

Medullary thyroid carcinoma (MTC) is a neuroendocrine tumor (NET), which originates in neural crest-derived calcitonin-producing C-cells. It occurs either sporadically or as a result of a germline mutation in the RET proto-oncogene, as in multiple endocrine neoplasia (MEN) syndrome type 2A including its variant familial MTC (FMTC) and type 2B. Currently, the only curative treatment for MTC is surgery, accompanied by lymph node dissection. However, the outcome is largely dependent on disease staging, with lymph node and distant metastases often identified at diagnosis, particularly in sporadic forms. Furthermore, the presence of cervical lymph node invasion at surgery predicts residual disease. The development of new treatments is strongly motivated by: (a) the low surgical cure rate when cervical lymph node metastases are present at the time of initial surgery, with 90% of patients having residual disease, (b) the high prevalence of distant metastases at initial diagnosis (lungs, bones and liver) and (c) the poor outcome in patients receiving cytotoxic chemotherapeutic agents. Herein, we focus on current nonsurgical options and perspectives in the treatment of MTC with emphasis on last year’s FDA-approved tyrosine kinase inhibitors (TKIs) and other systemic therapies that need to be considered in the setting of advanced disease

The crosstalk between insulin resistance, systemic inflammation, redox imbalance and the thyroid in subjects with obesity

We aimed at assessing the interaction between visceral adipose tissue (VAT), insulin resistance (IR), circulating levels of monocyte chemoattractant protein-1 (MCP-1) and malondialdehyde (MDA) and the thyroid parameters in obese subjects. Methods. Obese subjects without thyroid pathologies or diseases associated with systemic inflammation and OS were recruited. Insulinemia, visceral fat thickness, metabolic and thyroid parameters were assayed. Circulating levels of MCP-1 and MDA were used to quantify inflammation and OS. Results. A number of 160 obese subjects were included. The MCP-1 level increased with the degree of obesity and HOMA-IR. MCP 1 was positively associated with antithyroperoxidase antibody (TPOab) levels and the frequency of Hashimoto’s thyroiditis (HT). The MDA level was positively correlated with the degree of obesity, aspartate aminotransferase and MCP-1. MDA was an independent predictor for the occurrence of hypothyroidism. IR patients showed higher fT3 levels and a positive association between insulin and TPOab levels. Conclusions. Systemic inflammation increased with VAT, IR and OS and was correlated with the frequency and the severity of HT, suggesting that, in obesity, MCP-1 could be part of the etiopathogenesis of autoimmune thyroiditis. MDA was an independent risk factor for hypothyroidism; therefore, redox imbalance associated with obesity can produce cell damage and thyroid dysfunction. FT3 is increased in IR patients, thus being a marker for the severity of metabolic impairment

DIFFERENT INDICATIONS, ONE PROCEDURE: THYROIDECTOMY (AS SIMPLE AS THAT)

Introduction. Thyroidectomy is currently a rather simple procedure with various indications, regardless total or subtotal/near total, based on conventional approach or modern like robotic (trans-axillary and axillobreast robotic). We aim to introduce a few scenarios in daily endocrine practice based on a pictorial essay. This is a cases series. Case 1 is a 59-year old female with recent subclinical thyrotoxicosis with an extremely large multinodular goitre who was confirmed benign by the pathological report was provided after. Case 2 is a 70-year old female who self detected through palpation a large left thyroid macronodule with suspected ultrasound features. However, she still delays thyroidectomy. Case 3 is a 51-year old female also with compressive symptoms due multinodular goitre and a dominant left lobe nodule who was referred to surgery. Case 4 is a 59-year female treated with thiamazole for 12 years presents a large multinodular goitre which was referred to surgery. Conclusion. Different scenarios are ending with the idea of thyroidectomy from compressive local symptoms, to curative option for a potential malignancy etc

Gamma Knife radiosurgery: effect on corticotropin-secreting pituitary adenoma

Introduction: Cushing's disease (CD) is a complex endocrine disorder characterized by an increased risk of recurrence and persistence of hypercortisolism after initial transsphenoidal adenomectomy, a situation requiring alternative therapeutic measures. Case presentation: A 21-year-old female patient was admitted for weight gain with centripetal fat distribution, transient headache, hair thinning and psycho-emotional lability. Clinical examination revealed round facies, acne, purple-red striae, hirsutism with a Ferriman-Gallwey score of 20. The hormonal profile revealed high serum cortisol (of 283.1 ng/mL, normal:70-225 ng/mL) and high ACTH (Adrenocorticotropic Hormone) levels (of 260.6 pg/mL, normal: 7.2-63.3 pg/mL). The pituitary MRI (Magnetic Resonance Imaging) examination found a 4.3/4.4/6.2mm left paramedian microadenoma. The persistence of hypercortisolism after adenomectomy required GKRS (Gamma Knife radiosurgery). Four months after radiosurgery, complete remission of the disease was achieved and it was maintained at the last evaluation. At present, the patient is 20 weeks pregnant. Conclusions: Gamma Knife radiosurgery offers a high control rate of pituitary adenomas and a reasonable rate of remission of residual hypercortisolism after neurosurgical treatment. After surgery or GKRS, periodic monitoring is necessary for patients with CD due to the risk of pituitary insufficiency or relapse

Chronic autoimmune thyroiditis and obesity

Chronic autoimmune thyroiditis (Hashimoto’s thyroiditis) is the most common cause of hypothyroidism which may associate weight increase and changes in serum lipid levels. There is still controversy over the link between obesity and autoimmune hypothyroidism. The paper aims to assess obesity and lipid metabolism in patients with Hashimoto’s thyroiditis, and to establish a correlation between TSH (thyroid-stimulating hormone), FT4 (free thyroxine) levels, and the titer of antithyroid antibodies

Vanishing testes syndrome-related osteoporosis and high cardio-metabolic risk in an adult male with long term untreated hypergonadotropic hypogonadism

SUMMARY The male hypogonadism-related bone mass loss is often under diagnosed. Peak bone mass is severely affected if the hypogonadism occurs during puberty and is left untreated. We present an interesting; almost bizarre case of a male with non-functional testes early during childhood and undiagnosed and untreated hypogonadism until his fifth decade of life. Forty six year male is referred for goitre, complaining of back pain. Phenotype suggested intersexuality: gynoid proportions, micropenis, no palpable testes into the scrotum, no facial or truncal hair. His medical history had been unremarkable until the previous year when primary hypothyroidism was diagnosed and levothyroxine replacement was initiated. Later, he was diagnosed with ischemic heart disease, with inaugural unstable angina. On admission, the testosterone was 0.2 ng/mL (normal: 1.7-7.8 ng/mL), FSH markedly increased (56 mUI/mL), with normal adrenal axis, and TSH (under thyroxine replacement). High bone turnover markers, and blood cholesterol, and impaired glucose tolerance were diagnosed. The testes were not present in the scrotum. Abdominal computed tomography suggested bilateral masses of 1.6 cm diameter within the abdominal fat that were removed but no gonadal tissue was confirmed histopathologically. Vanishing testes syndrome was confirmed. The central DXA showed lumbar bone mineral density of 0.905 g/cm2, Z-score of -2.9SD. The spine profile X-Ray revealed multiple thoracic vertebral fractures. Alendronate therapy together with vitamin D and calcium supplements and trans-dermal testosterone were started. Four decades of hypogonadism associate increased cardiac risk, as well as decreased bone mass and high fracture risk

PLUMMER THYROID ADENOMA: BACK TO THE BASIC

Plummer disease of the thyroid represents a traditional condition causing primary hyperthyroidism. Our aim is to introduce a short overview regarding the use of the term “Plummer adenoma” of the thyroid and to report a case with traditional diagnosis. In terms of method this is a case report and a historical data report using as references PubMed and online sites of general endocrine and historical information. This is a 43-year old female who had 2 months ago a mild episode of vertigo, followed by intermittent sweating and weight loss (2 kilos within 2 months). Hyperthyroidism is confirmed based on suppressed TSH. Thyroid scintigrame was performed using as thyroid tracer Tc99 Perthechnetate which revealed thyroid with normal anatomy with a “hot” autonomous nodule at the level of right thyroid lobe. Thyroid ultrasound showed a right lobe of 2.4 by 3.2 by 3.5 cm and a left lobe of 1.1 by 0.8 by 3.6 cm. Right lobe has a macronodule of 3.5 by 2.1 by 2.8 cm which entirely occupies the lobe; it has an inhomogeneous pattern, with microcalcifications and tracheal effect to the opposite site. The patient was offered daily thiamazole and a low dose of beta blockers; follow-up is necessary; then the indication of thyroidectomy will be done because of thyroid dimensions and nodule aspect in association with tracheal effect. Plummer toxic nodule of the thyroid represents a classical endocrine condition which requires thyroid scintigrame to be adequately identified even the management is not distinctive from other forms of primary hyperthyroidism

PALE SKIN: AN ADRENAL CANCER?

Adrenal carcinoma is a complex orphan disease with a very poor prognosis. The evolution is rapid and in cases with suggestive symptoms the diagnosis may be established earlier in order to improve the outcome. One third of the patients are negative for a clear hormonal expression or they have an atypical presentation. We introduce an adult patient diagnosed with adrenal carcinoma and a rapid lethal outcome who initially presented with pale skin and non-specific abdominal pain. A multidisciplinary team is essential for adequate diagnosis and prompt intervention. Severe bleeding at the level of the adrenal carcinoma causing symptomatic anaemia is a rare event. The prognosis in adrenocortical carcinoma is severe and the presence of humoral hypercalcemia represents a sign of short survival time

FROM TRANSITORY ERYTHEMA TO PHEOCROMOCYTOMA

This is a case report of a female with transitory erythema who was found with thrombocytosis caused by a pheocromocytoma. The skin changes were not accompanied by typical manifestations of an adrenergic crisis although she had high blood pressure episodes without skin colour changes. Both the erythema and the arterial hypertension controlled after the adrenal tumour was removed. Pheocromocytoma associates not only the excessive production of metanephrines and normetanephrines but also other factors like interleukins (for instance, IL-6, causing a general inflammatory syndrome including reactive thrombocytosis) eritropoietin or parathormone related peptide. Thrombocytosis is extremely rare associated with cathecolamines producing tumour and it may become a supplementary contributor to cardiovascular risk