Difficult Diagnosis and Management of Concealed Cushing.

BACKGROUND: Adrenocorticotropic Hormone (ACTH)-secreting tumors account for 5- 10% of Cushing syndrome cases and are often difficult to diagnose and treat. CASE REPORT: A 44-year-old man presented with arterial hypertension and weight gain. On the physical examination, he exhibited central obesity, abdominal striae rubrae, and facial plethora. Due to the clinical suspicion of Cushing syndrome, the Nugent test and Liddle-1 test were performed, which showed a lack of cortisol suppression. ACTH levels were also high (138 pg/mL), so pituitary MRI and dynamic tests were performed, including the Corticotropin-releasing Hormone (CRH) stimulation test and Liddle-2. MRI showed a 3 mm pituitary microadenoma, but hormonal testing suggested ectopic ACTH production. Chest CT detected a 10-mm nodule in the upper lobe of the right lung, suspicious for a carcinoid tumor. However, the nodule did not exhibit any enhancement on 68-Gallium-DOTATOC PET-CT, and further, 18-FDG PET-CT was inconclusive. In addition, the nodule was deemed non-biopsiable due to its location. Meanwhile, the patient developed osteoporosis, resulting in two vertebral fractures and one rib fracture, which was treated with zoledronate. Furthermore, the patient developed acute aortic insufficiency. During bioprosthetic valve replacement, the thoracic surgeon performed wedge resection of the right upper lung lobe. The histological examination of the lesion revealed a typical lung carcinoid (1.2x0.9 cm, pT1bNXR0, Ki671%, ACTH positive in 95% of neoplastic elements). ACTH levels dropped to 4 pg/mL on the fourth postoperative day. CONCLUSION: ACTH-secreting tumors are particularly challenging diseases. A comprehensive hormonal and instrumental valuation is often required, necessitating a multidisciplinary approach.

Thyroid function tests, incongruent internally and with thyroid status, both in a pregnant woman and in her newborn daughter.

Introduction: Thyroid function tests (TFT) are extensively used in daily clinical practice. Here, we described a case of incongruent TFT both in a pregnant woman and in her newborn. Case presentation: A 32-year-old woman, diagnosed with autoimmune thyroiditis during her first pregnancy, was monitored during her second gestation. At week 5 + 2 days, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) values (Dimension VISTA 1500, Siemens Healthineers) were within normal limits. At week 19 + 5 days, TSH remained normal while FT4 increased approximately by three-fold. FT4 inconsistency was with both TSH and the clinical status since she continued to be clinically euthyroid. On the same serum sample, thyroid autoantibodies were negative. At week 25 + 4 days, the patient complained of palpitations and dyspnea, with tachycardia. Even though TSH was normal, high levels of both FT4 and free triiodothyronine (FT3) were interpreted as evidence of thyroid overactivity and methimazole was started. TFT of the pregnant woman continued to be monitored throughout gestation. Postpartum FT4 and FT3 gradually returned to normal. TFT, performed on the daughter's serum, 3 days after birth, showed the same inconsistency as her mother but without clinical signs of congenital hyperthyroidism. Based on the clinical and laboratory setting, the presence of circulating autoantibodies against T3 and T4 (THAb) was suspected and demonstrated by radioimmunoprecipitation. Conclusion: Analytical interferences should be supposed when TFT do not fit with the clinical picture and despite their infrequency, THAb must also be considered. To our knowledge, this is the first case describing the passage of THAb to the newborn.

A Retrospective Cohort Study of Histology-Proven Neuroendocrine Neoplasms in the Italian Area of Udine.

AIMS: The aim of this study was to investigate the epidemiology of histology-proven Neuroendocrine neoplasms (NENs) in an Italian area. BACKGROUND: NENs are a rare and poorly known disease and the global incidence and prevalence appear to be increasing over the past decades. OBJECTIVE: The objectives of this study were to estimate the incidence and trends of NENs in a 250,000-inhabitant area in the North-East of Italy in the 1998-2018 period and to compare them with international data. METHODS: This retrospective cohort study was based on the analysis of anonymous health administrative databases, linked with each other at individual patient level through an anonymous stochastic key. NENs were identified from the anatomical pathology database. The standardized incidence rate (2010ESP and US2000) ± 95% CI per 100,000 were calculated, both annually and globally, for the whole period. Incidence was also calculated for specific anatomical sites and by gender. Trends for the considered periods and sites were summarized through the annual percent change (APC) and average increase (cases per 100,000 per year). RESULTS: In the 1998-2018 period, the standardized incidence rate of NENs in the area of Udine was 2.49 (APC 3.33). A total of 162 cases were observed (51.2% males). Differences in incidence and trend were observed between sexes. The obtained results were consistent with those reported in other countries, confirming a significant and steady increase in NENs incidence in the last twenty years. CONCLUSION: This study provides new epidemiological data on NENs in Italy. The observed sex differences deserve further investigations.

Mazabraud's Syndrome: A Case Report and Up-To-Date Literature Review.

OBJECTIVE: Mazabraud's syndrome is a rare form of bone fibrous dysplasia associated with intramuscular myxomas. Fibrous dysplasia, is generally localized to pelvis and femur and it results in a fragile bone with deformities, pain, pathological fractures and functional impairment. Intramuscular myxomas, are rare benign mesenchymal neoplasms that exceptionally may evolve to malignant forms. METHODS: This case report describes a 66-year-old woman with Mazabraud's Syndrome (MS), characterized both by monostotic right femur fibrous dysplasia and by a solitary intramuscular myxoma at the right quadriceps muscle, that underwent a long-term treatment (4 years) with intravenous zoledronic acid. RESULTS: Zoledronic acid therapy rapidly lowered bone pain together with a reduction of intramuscular myxoma volume, but did not affect the extension of fibrous dysplasia. No adverse effects have been observed during treatment. CONCLUSION: Highly active bisphosphonates are commonly used for the treatment of bone metabolic disorders and they are generally well tolerated. Zoledronic acid may represent a promising alternative to surgical intervention in MS, although its use in rare form of bone fibrous dysplasias is still controversial.

An Unusual Case of Medullary Thyroid Carcinoma and A Revision of Current Literature.

BACKGROUND: Medullary thyroid cancer (MTC) accounts for 5% of all thyroid cancers and occurs either sporadically or in a hereditary pattern. Routine calcitonin (CT) measurement is suggested for MTC screening in patients with nodular thyroid disease. PATIENT FINDINGS: A 45 years-old woman incidentally discovered, with neck ultrasound, the presence of thyroid micronodules. Fine-needle aspiration (FNA) on thyroid prevailing nodule did not demonstrate cellular atypia. During follow-up, FNA was repeated on the previously analyzed nodule suspicious for Hürthle cell nodule suspicious for follicular neoplasm and on another hypoechoic right nodule which showed cellular atypia. CT was <2 pg/ml (normal values <18.2 pg/ml), anti-thyroid antibodies were positive and the patient showed a normal thyroid function. The patient also was diagnosed with primary hyperparathyroidism with an enlarged parathyroid gland behind the right thyroid lobe. Therefore, she underwent total thyroidectomy and a selective parathyroidectomy was performed. Histology showed an encapsulated microMTC (pT1aNxMx) associated with diffuse C-cell hyperplasia and lymphocytic thyroiditis. The neoplasm was positive for calcitonin and chromogranin A and negative for thyroglobulin. A right parathyroid adenoma was also diagnosed. One month after surgery basal and stimulated CT were <2 ng/ml. Genetic analysis did not reveal mutation of RET proto-oncogene. Twelve months after surgery, neck ultrasonography, chest and abdomen computed tomography did not demonstrated residual/recurrent disease with undetectable serum CT. CONCLUSION: In the literature, few MTC cases with normal serum CT have been reported. Although MTC without elevated plasma CT is extremely rare, normal or low CT levels, do not entirely exclude this diagnosis.

Shift from Levothyroxine Tablets to Liquid Formulation at Breakfast Improves Quality of Life of Hypothyroid Patients.

BACKGROUND: Until recently, treatment of hypothyroidism has been accomplished using monotherapy of synthetic L-thyroxine (L-T4) sodium tablets that should be taken 30-60 minutes before breakfast. Nowadays, a liquid preparation of levothyroxine is available and can effectively replace tablets without the need of waiting before having breakfast. Evidence of Quality of life (QoL) improvement when shifting from the former to the latter preparation, however, is still lacking. OBJECTIVE: The study aimed to assess changes in QoL of hypothyroid patients dissatisfied with their therapy with L-T4 sodium tablets who were switched from tablets taken 30-60 minutes before breakfast to liquid L-T4 at breakfast. METHODS: A total of 418 consecutive hypothyroid subjects treated by means of L-T4 tablets were asked about their satisfaction/dissatisfaction in order to take the medication 30-60 minutes before having breakfast. Overall, 110 patients (26.3%) complained of the timing of their L-T4 therapy (30-60 minutes before breakfast). A dedicated QoL questionnaire (ThyTSQ), taking just a few minutes to be filled in was then administered to these dissatisfied patients. They were therefore switched to L-T4 to be taken at breakfast. Aiming to avoid TSH elevation due to L-T4 tablets malabsorption caused by meal interference and gastric pH changes, patients were invited to take L-T4 liquid form, as this is claimed to be scarcely affected by the non-fasting state. The questionnaire (ThyTSQ) was administered again at the control visit 3 months later. TSH, FT4, FT3 serum concentrations and metabolic parameters were also recorded. RESULTS: An improved QoL, mainly due to an easier adherence to treatment, was reported by 66.6% of 102 patients who completed the study after shifting from taking medication 30-60 minutes before breakfast to at breakfast ingestion (P<0.01). An overall 10.7% of patients found the liquid formulation distasteful. Mean values of TSH, FT4, FT3, and of metabolic parameters did not significantly change but in eight patients (7.7%) who showed a TSH increase > 2mIU/L. CONCLUSION: In hypothyroid subjects dissatisfied with L-T4 tablets ingested 30-60 minutes before breakfast, the shift to the same dose of L-T4 in liquid form taken at breakfast improved QoL in the majority of patients, without affecting thyroid function.

Delayed risk stratification, to include the response to initial treatment (surgery and radioiodine ablation), has better outcome predictivity in differentiated thyroid cancer patients.

INTRODUCTION: After initial treatment, differentiated thyroid cancer (DTC) patients are stratified as low and high risk based on clinical/pathological features. Recently, a risk stratification based on additional clinical data accumulated during follow-up has been proposed. OBJECTIVE: To evaluate the predictive value of delayed risk stratification (DRS) obtained at the time of the first diagnostic control (8-12 months after initial treatment). METHODS: We reviewed 512 patients with DTC whose risk assessment was initially defined according to the American (ATA) and European Thyroid Association (ETA) guidelines. At the time of the first control, 8-12 months after initial treatment, patients were re-stratified according to their clinical status: DRS. RESULTS: Using DRS, about 50% of ATA/ETA intermediate/high-risk patients moved to DRS low-risk category, while about 10% of ATA/ETA low-risk patients moved to DRS high-risk category. The ability of the DRS to predict the final outcome was superior to that of ATA and ETA. Positive and negative predictive values for both ATA (39.2 and 90.6% respectively) and ETA (38.4 and 91.3% respectively) were significantly lower than that observed with the DRS (72.8 and 96.3% respectively, P<0.05). The observed variance in predicting final outcome was 25.4% for ATA, 19.1% for ETA, and 62.1% for DRS. CONCLUSIONS: Delaying the risk stratification of DTC patients at a time when the response to surgery and radioiodine ablation is evident allows to better define individual risk and to better modulate the subsequent follow-up.

Lack of association between urinary iodine excretion and successful thyroid ablation in thyroid cancer patients.

BACKGROUND: Low-iodine diet is prescribed before (131)I administration in patients with differentiated thyroid cancer, although no study has properly quantified its clinical benefit. OBJECTIVE: Our study aimed to evaluate the association between urinary iodine excretion (UIE) and (131)I ablation by correlating UIE with the rate of successful ablation. PATIENTS: We retrospectively studied 201 differentiated thyroid cancer patients who had received (131)I therapy and posttherapy whole-body scan (WBS) for remnant ablation after either thyroid hormone withdrawal (THW group, n = 125) or recombinant human TSH (rhTSH group, n = 76). The outcome of thyroid ablation was assessed using two different criteria: no visible uptake at control WBS 8-12 months after ablation or no visible uptake plus undetectable stimulated serum thyroglobulin (Tg). RESULTS: According to the criterion of no visible uptake, 84.6% of the patients were successfully ablated, with no significant difference between THW and rhTSH groups. Mean UIE at the time of ablation was 132 +/- 160 microg/liter, not significantly different between patients of the THW and rhTSH groups. There was no significant difference in UIE between ablated or nonablated patients both in the whole group and the rhTSH or THW groups. According to the criterion of no visible uptake plus undetectable stimulated serum Tg (in anti-Tg negative patients) at control WBS 8-12 months after ablation, UIE was not significantly different in ablated and nonablated patients. CONCLUSIONS: Our study indicates that the body iodine content is not an important determinant of thyroid ablation, when preparing the patients with either THW or rhTSH.

A comparison of 1850 (50 mCi) and 3700 MBq (100 mCi) 131-iodine administered doses for recombinant thyrotropin-stimulated postoperative thyroid remnant ablation in differentiated thyroid cancer.

OBJECTIVE: Recently, a multicenter study in differentiated thyroid cancer (DTC) patients showed that 3700 MBq 131-iodine ((131)I) after recombinant human TSH (rhTSH) had a successful thyroid ablation rate similar to that obtained after thyroid hormone withdrawal. We investigated whether 1850 MBq (131)I had a similar successful rate to 3700 MBq in patients prepared with rhTSH. DESIGN: A total of 72 patients with DTC were randomly assigned to receive 1850 (group A, n = 36) or 3700 MBq (group B, n = 36) (131)I after rhTSH. One injection of 0.9 mg rhTSH was administered for 2 consecutive days; (131)I therapy was delivered 24 h after the last injection, followed by a posttherapy whole-body scan. Successful ablation was assessed 6-8 months later. RESULTS: Successful ablation (no visible uptake in the diagnostic whole-body scan after rhTSH stimulation) was achieved in 88.9% of group A and B patients. Basal and rhTSH-stimulated serum thyroglobulin was undetectable (<1 ng/ml) in 78.9% of group A and 66.6% of group B patients (P = 0.46). Similar rates of ablation were obtained in both groups also in patients with node metastases. CONCLUSION: Therapeutic (131)I activities of 1850 MBq are equally effective as 3700 MBq for thyroid ablation in DTC patients prepared with rhTSH, even in the presence of node metastases.