The ancient Greek poet Sappho and the first case report of the fight-or-flight response.

Sappho has always been regarded as one of the greatest lyric poets of ancient Greece. Her famous poem Fragment 31 V., also known as the "Ode to Jealousy", accurately describes the profound emotional reaction triggered by the sight of her beloved. The poet's precise description of each sign and symptom triggered by this arousal makes Sappho 31 V., to the best of our knowledge, the first analytical description of the acute stress response, the so-called "fight-or-flight" response, in human history. Here, Fragment 31 V. is re-read from a medical point of view, correlating the ancient Greek lyric text, the corresponding medical terms, and the underlying catecholamine mechanism of action.

Effect of vitamin D supplementation on TSH levels in euthyroid subjects with autoimmune thyroiditis.

PURPOSE: The impact of vitamin D supplementation on thyroid function is not clear and the relationship between hypovitaminosis D and autoimmune thyroiditis (ATD) incidence and evolution is still a matter of debate. The aim of this study was to retrospectively evaluate the impact of vitamin D supplementation on thyroid function in subjects with and without ATD. METHODS: One hundred and ninety-eight euthyroid subjects, with diagnosis of "hypovitaminosis D" (<30 ng/mL) who had been taking supplementation therapy with cholecalciferol for different time periods, were included. They were divided in two groups according to the previous diagnosis of ATD: "ATD-neg" group including subjects without ATD [n = 103 (52%)]; "ATD-pos" group including subjects with a confirmed diagnosis of ATD [n = 95 (48%)]. For both groups, we considered TSH and 25 hydroxyvitamin D (25OHD) levels before (T0) and after (T1) cholecalciferol supplementation. We also considered the treatment duration and the monthly dose of cholecalciferol expressed as IU/month. RESULTS: In hypovitaminosis D subjects with ATD, TSH levels significantly decreased after therapy with cholecalciferol 100.000 IU/month [mean ± SD, TSH at T0: 2.67 ± 1.21 vs. TSH at T1: 2.28 ± 0.86, p = 0.028]. No significant TSH variation was observed in ATD-neg group, irrespective of treatment dose and duration. As expected, 25OHD levels significantly improved with all monthly doses and especially in the group receiving 100.000 IU/month. CONCLUSIONS: Cholecalciferol supplementation improved thyroid function in euthyroid ATD-pos subjects affected with severe hypovitaminosis D. In particular, a significant reduction in TSH levels was observed in subjects with very low baseline 25OHD levels, after taking high monthly doses of cholecalciferol.

Lenvatinib for thyroid cancer treatment: discovery, pre-clinical development and clinical application.

Introduction: About one third of patients affected with thyroid cancer present with recurrent disease. Unresectability, advanced disease and radioiodine refractoriness are considered poor prognostic factors. Treatment with small molecules inhibiting molecular signaling can be considered for patients with progressive disease, when other therapeutic strategies cannot be applied. Lenvatinib is a tyrosine kinase inhibitor targeting multiple molecular factors involved in angiogenesis and tumor progression. Preclinical studies have demonstrated the utility of lenvatinib as a targeted therapy for different tumors, including both differentiated and anaplastic thyroid cancer.Areas covered: The authors provide an overview of the preclinical development of lenvatinib in the treatment of thyroid cancer and review its clinical application. They also provide their expert opinion on its development.Expert opinion: Preclinical studies have helped in the understanding of the mechanisms of thyroid carcinogenesis and in the development of a targeted therapy. These findings have represented the rationale for the use of lenvatinib in clinical trials, which have confirmed its utility but yet failed to prove a clear benefit in overall survival. The decision to start a systemic treatment with lenvatinib must be personalized for each patient evaluating the risk/benefits ratio. Treatment emergent adverse events must be considered and reasonably managed by a multidisciplinary approach.

Combined systemic (fluconazole) and topical (metronidazole + clotrimazole) therapy for a new approach to the treatment and prophylaxis of recurrent candidiasis.

Recurrent vulvovaginal candidiasis (RVVC) is an important pathological and infectious condition that can greatly impact a woman's health and quality of life. Clinical and epidemiological studies show that different types of therapies are able to eliminate the signs and symptoms of mycotic vaginitis in the acute phase, but so far none of these has proved able to significantly reduce the risk of long-term recurrence. In this review, based on the available literature and original data from a preliminary in-vitro microbiological study on the compatibility between fluconazole, clotrimazole and metronidazole a new therapeutic approach to RVVC is discussed and presented. The treatment proposed is a combined scheme using both systemic antimicrobial drug therapy with oral fluconazole 200 mg and topical drug therapy using the association metronidazole 500 mg and clotrimazole 100 mg (vaginal ovules) with adjuvant oral probiotic therapy. In detail, at the time of diagnosis in the acute symptom phase, we propose the following treatment scheme: fluconazole 200 mg on day 1, 4, 11, 26, then 1 dose/month for 3 months at the end of the menstrual cycle; plus metronidazole/clotrimazole ovules 1/day for 6 days the first week, then 1 ovule/day for 3 days the week before the menstrual cycle for 3 months; plus probiotic 1 dose/day for 10 days for 3 months starting from the second month to the end of the menstrual cycle. This scheme aims to address the recurrent infection aggressively from the outset by attempting not only to treat acute symptoms, but also to prevent a new event by countering many of the potential risk factors of recurrence, such as the intestinal Candida reservoir, the mycotic biorhythm, the formation of biofilm, the phenotype switching and the presence of infections complicated by the presence of C. non albicans or G. Vaginalis, without interfering, but rather favoring the restoration of the vaginal lactobacillus species. Future clinical studies will be useful to confirm the proposed scheme.

Effects of a new combination of plant extracts plus d-mannose for the management of uncomplicated recurrent urinary tract infections.

Urinary tract infections (UTIs) are an economic burden for public health. The increasing prevalence of resistant bacteria which cause UTIs may be related to the inappropriate prescription of antibiotics. The aim of this preliminary study was to evaluate whether three different combinations of plant extracts plus d-mannose are effective in preventing the recurrence of UTIs. Three groups of patients received three combinations of plant extracts in conjunction with d-mannose. These were: berberine, arbutin and birch (group A); berberine, arbutin, birch and forskolin (group B); and proanthocyanidins (group C). The clinical recurrence of cystitis at the end of treatment and during follow-up was determined by comparison with baseline measurements using the microbiological assessment of urine samples, vaginal swabs and vaginal smear slides. Patients in groups A and B had a lower incidence of episodes of recurrent cystitis during treatment and follow-up, samples with a significantly lower median bacterial load and a reduction of the grade of lactobacillary flora compared to patients in group C.

A rare case of juvenile hypertension: coexistence of type 2 multiple endocrine neoplasia -related bilateral pheochromocytoma and reninoma in a young patient with ACE gene polymorphism.

BACKGROUND: Pheochromocytoma and reninoma represent two rare diseases causing hypertension. We here reported a rare case of association between type 2 multiple endocrine neoplasia related bilateral pheochromocytoma and reninoma. Moreover, polymorphism of ACE gene, which is known to be related to an increase of cardiovascular risk, has been found in the same patient. CASE PRESENTATION: A 24 year old Caucasian man came to our attention for severe hypertension, resistant to anti-hypertensive polytherapy. At the age of twenty he had undergone total thyroidectomy with lymphadenectomy for medullary carcinoma. Genetic testing showed a RET mutation of codon 918 (exon 16) not documented in other family members. During the follow-up, a progressive increase of urinary metanephrines and catecholamines was recorded. Our evaluation confirmed the presence of severe hypertension (220/140 mmHg) and a severe increase of urinary catecholamines and metanephrines. Due to the presence of hypokalemia, other causes of hypertension were researched leading to the discovery of hyperreninemia (236 µUI/ml) with mild hyperaldosteronism, and a mild increase of the renal artery resistance at ultrasound. An abdominal MRI showed multiple adrenal masses and a right kidney nodular lesion of about 2 cm. The patient underwent bilateral adrenalectomy and right nephrectomy, and histology confirmed the presence of bilateral pheochromocytoma and right reninoma. The post-surgery laboratory evaluation showed a rapid reduction of the urinary metanephrines while plasma renin level remained low in spite of the bilateral adrenalectomy without any mineralocorticoid supplementation. To further investigate these unusual feature, we performed genetic testing for the ACE gene, which revealed the presence of ACE I/D polymorphism. CONCLUSION: This unique report describes the association between two rare causes of hypertension in the same patient. Furthermore, the absence of requirement of mineralocorticoid supplementation in spite of bilateral adrenalectomy, represent an uncommon and interest finding.

Iodine Supplementation: Usage "with a Grain of Salt".

Iodine supplementation through salt iodization is a worldwide, effective strategy for preventing iodine deficiency-related problems. Its safety and efficacy profile has been extensively investigated, and benefits far outweigh the potential iodine-induced risks. Moreover, iodine supplementation during pregnancy in order to avoid brain damage in the newborn is considered a mainstay of preventive medicine. Exposure to high amounts of iodine is actually well tolerated in most cases and can be unrecognized. Nevertheless, at-risk individuals may develop thyroid dysfunction even when they are exposed to increases in iodine intake universally considered as safe. Iodine-induced thyroid disorders include thyroid autoimmunity, thyrotoxicosis, iodine-induced goiter, and hypothyroidism. Moreover, a relationship between iodine intake and histotype distribution of differentiated thyroid cancer has been observed, with a progressive shift from follicular to papillary thyroid cancer. To date, evaluating iodine status in a clinical setting has limitations, and assessing the actual risk for each individual can be challenging, since it is influenced by personal history, genetics, and environmental factors. In conclusion, iodine supplementation programs need to be continued and strengthened, but iodine should be used "with a grain of salt," because a growing number of susceptible individuals will be exposed to the risk of developing iodine-induced thyroid disorders.

Post-surgery severe hypocalcemia in primary hyperparathyroidism preoperatively treated with zoledronic acid.

Zoledronic acid is a newly FDA-approved bisphosphonate for the treatment of hypercalcemia of malignancy. Although the safety and efficacy of this drug in treating hypercalcemia associated with hyperparathyroidism have not yet been established in clinically controlled trials, its off-label use is not uncommon. We describe a patient with primary hyperparathyroidism treated with zoledronic acid who developed severe postoperative hypocalcemia. A 64-yr-old woman was admitted with severe hypercalcemia. She was treated with rehydration, calcitonin, methylprednisolone, furosemide as well as 4 mg/day of zoledronic acid for two consecutive days. Primary hyperparathyroidism caused by a right inferior parathyroid lesion was diagnosed. While awaiting surgery, she continued furosemide, methylprednisolone and hydration: after one week, serum calcium had fallen to such a low level that a short-term calcium carbonate supplementation was required. Three weeks after admission, the patient underwent selective right inferior parathyroidectomy, followed by reduction of PTH. During the postoperative period the patient presented severe hypocalcemia resistant to the usual treatment. Serum calcium levels returned to normal three months after surgery. The severity of hypocalcemia and the resistance to conventional treatments suggest that the effect of hungry bone syndrome could be worse in patients treated with bisphosphonates in the preoperative phase.

Hypothyroidism related to tyrosine kinase inhibitors: an emerging toxic effect of targeted therapy.

Despite their inherent selectivity, targeted therapies such as tyrosine kinase inhibitors (TKIs) can cause unusual adverse effects. Sunitinib and sorafenib are multitargeted TKIs that have been demonstrated to induce hypothyroidism and thyroid dysfunction. Retrospective studies indicate that sunitinib can induce hypothyroidism in 53-85% of patients, and in prospective studies this complication has been reported in 36-71% of patients. Sorafenib has been reported to be responsible for hypothyroidism in 18% of patients with metastatic renal-cell carcinoma. Furthermore, imatinib and sunitinib seem to increase the requirement of levothyroxine in hypothyroid patients. The management of thyroid dysfunction and possible related symptoms, such as fatigue, represents a challenge to oncologists. We propose a diagnostic and therapeutic algorithm for the management of TKI-related hypothyroidism. Prospective trials are needed to define the incidence of overt and subclinical hypothyroidism and thyroid dysfunction during therapy with sunitinib, sorafenib and potentially other TKIs. The safety and efficacy, and optimal dosing and timing of starting replacement therapy in patients affected by TKI-related hypothyroidism need accurate appraisal and should be evaluated prospectively in appropriately designed trials.