A case of celiac plexus block causing iatrogenic Cushing's syndrome.

Treatment with corticosteroids can lead to iatrogenic Cushing's syndrome when used for longer intervals and in high doses. Less common administration routes may conceal the exposure, raising the possibility of misdiagnosis and mismanagement.

A Middle-aged Woman With Recurrent Intrathyroidal Parathyroid Cyst Treated With Ethanol Sclerotherapy.

Background/Objective: Parathyroid cysts (PC) are a rare cause of cervical masses, with an ectopic intrathyroidal location being even more rare, with only 9 cases reported in the literature. We present a case of a recurrent intrathyroidal cyst successfully treated with ethanol sclerotherapy. Case Report: A 64-year-old woman presented to our clinic in 2017 with a cervical prominence and recurrent pressure sensation in her left lower neck. She had a history of multiple cyst aspiration drainage procedures for a recurrent intrathyroidal PC. Ultrasound revealed a simple cyst measuring 5.1 cm × 2.1 cm × 1.7 cm encompassing most of the left thyroid lobe. Parathyroid hormone level in the cyst fluid was elevated, but serum calcium and parathyroid hormone levels were within normal range. To prevent additional recurrences, ethanol sclerosis of the cyst was performed. After 6 years of follow-up, the patient remains asymptomatic and without evidence of PC recurrence. Discussion: Although surgical resection of PC can be performed, in the case of an intrathyroidal PC, this would involve loss of functional thyroid tissue and the potential risk of postoperative hypothyroidism. Ethanol sclerosis has been successfully utilized to shrink both thyroid cysts and orthotopically positioned PCs while preserving thyroid tissue. In this case, ethanol sclerosis was used to successfully manage an intrathyroidal PC. Conclusion: Based on the excellent response in this case and reports of efficacy of sclerosis in orthotopically positioned PCs, we conclude that ethanol sclerotherapy seems to be an effective treatment option for recurrent intrathyroidal PCs.

A Parathyroid Hormone-Guided Calcium and Calcitriol Supplementation Protocol Reduces Hypocalcemia-Related Readmissions Following Total Thyroidectomy.

OBJECTIVE: To determine the effect of a 4-hour postoperative serum parathyroid hormone (PTH)-guided calcium (Ca) and calcitriol supplementation protocol on the incidence of hypocalcemia and hospital readmissions in patients undergoing total thyroidectomy. METHODS: This was a single-institution, retrospective chart review of patients who underwent total thyroidectomy; 148 and 389 of the patients underwent surgery prior to and after the protocol implementation, respectively. The risk of hypocalcemia was stratified as low (PTH level of >30 pg/mL), medium (15-30 pg/mL), and high (<15 pg/mL), using serum PTH values obtained 4 hours postoperatively. Hypocalcemia was defined as a total serum Ca level of <8 mg/dL. Baseline demographic and operative characteristics and postoperative outcome were recorded for both groups. The Fisher exact test and Wilcoxon rank sum test were used to compare the characteristics of the 2 groups. A multivariate logistic regression model was applied to account for potentially confounding variables. RESULTS: Postoperative hypocalcemia occurred significantly less frequently in the protocol group compared with that in the preprotocol group (10.3% vs 20.9%, P = .002). The reduction in hypocalcemia in the protocol group was observed in both patients with (16.3% vs 25.6%) and without (8.4% vs 19.3%) cervical lymph node dissection. The protocol group had a significantly lower incidence of hospital readmission events than the preprotocol group (1.0% vs 4.7%, P = .013). CONCLUSION: Compared with a historical cohort, a PTH-guided protocol for Ca and calcitriol supplementation significantly reduces the postoperative hypocalcemia and hospital readmission rates in patients undergoing total thyroidectomy.

Continuous Glucose Monitoring for Patients with COVID-19 Pneumonia: Initial Experience at a Tertiary Care Center.

OBJECTIVE: Patients hospitalized with COVID-19 and hyperglycemia require frequent glucose monitoring, usually performed with glucometers. Continuous glucose monitors (CGMs) are common in the outpatient setting but not yet approved for hospital use. We evaluated CGM accuracy, safety for insulin dosing, and CGM clinical reliability in 20 adult patients hospitalized with COVID-19 and hyperglycemia. METHODS: Study patients were fitted with a remotely monitored CGM. CGM values were evaluated against glucometer readings. The CGM sensor calibration was performed if necessary. CGM values were used to dose insulin, without glucometer confirmation. RESULTS: CGM accuracy against glucometer, expressed as mean absolute relative difference (MARD), was calculated using 812 paired glucometer-CGM values. The aggregate MARD was 10.4%. For time in range and grades 1 and 2 hyperglycemia, MARD was 11.4%, 9.4%, and 9.1%, respectively, with a small variation between medical floors and intensive care units. There was no MARD correlation with mean arterial blood pressure levels, oxygen saturation, daily hemoglobin levels, and glomerular filtration rates. CGM clinical reliability was high, with 99.7% of the CGM values falling within the "safe" zones of Clarke error grid. After CGM placement, the frequency of glucometer measurements decreased from 5 to 3 and then 2 per day, reducing nurse presence in patient rooms and limiting viral exposure. CONCLUSION: With twice daily, on-demand calibration, the inpatient CGM use was safe for insulin dosing, decreasing the frequency of glucometer fingersticks. For glucose levels >70 mg/dL, CGMs showed adequate accuracy, without interference from vital and laboratory values.

When a "Low T" Diagnosis Can Be the Clue to a More Complex Problem.

Male hypogonadism remains a poorly evaluated and managed clinical condition despite the availability of clinical guidelines. We present a case of a male patient diagnosed with secondary hypogonadism related to partial empty sella syndrome, whose clinical course was complicated by a hypotensive near-syncopal event. Although initial hypopituitarism symptoms could be subtle and nonspecific and could involve only one hormonal axis, a thorough evaluation of the pituitary function may identify additional deficiencies such as a subclinical chronic adrenal insufficiency that may become manifest during situations of increased physiological stress with potential life-threatening consequences.

Update on the Evaluation of Thyroid Nodules.

Thyroid nodules (TN) are prevalent in the general population and represent a common complaint in clinical practice. Most are asymptomatic and are associated with a 7%-15% risk of malignancy (1). Methods: PubMed and Medline were searched for articles with a focus on the epidemiology, diagnosis, and management of TN over the past 5 y. Results: The increase in frequency of imaging has led to a rise in the incidence of incidentally diagnosed TN. The initial evaluation of a TN includes assessing thyroid function, clinical risk factors, and neck imaging. Ultrasound remains the gold standard for assessing TN morphology, and biopsy is the standard method for determining whether a TN is benign. Recently published risk stratification systems using morphologic characteristics on ultrasonography have been effective in reducing the number of unnecessary biopsies. Advances in molecular testing have reduced the number of surgical procedures performed for diagnostic purposes on asymptomatic TN with indeterminate cytology. Scintigraphy is the first-line study for assessing a hyperfunctioning nodule. Many TN can be followed clinically or with serial ultrasound after the initial diagnosis. Surgical intervention is warranted when local symptoms are present, in patients with clinical risk factors, as well as in most situations with malignant cytology. Active surveillance is an option in cases of micropapillary thyroid cancer. Emerging nonsurgical approaches for treating TN include ethanol ablation for TN; sclerotherapy for thyroid cysts; and thermal techniques, such as radiofrequency ablation, laser ablation, microwaves, and high-intensity focused ultrasound. Conclusion: Most TN are benign and can be safely monitored. The indications for biopsy and frequency of imaging should be tailored on the basis of risk stratification. Treatment options should be individualized for each patient's particular situation. Active surveillance should be considered in certain cases of papillary microcarcinoma.

Patient Discomfort in Relation to Thyroid Nodule Fine-Needle Aspiration (FNA) Performed with or without Parenteral and/or Topical Anesthetic.

OBJECTIVE: There is much reported variation in the impact of local anesthesia on thyroid fine-needle aspiration (FNA) related discomfort. We compare patients undergoing thyroid FNA with subcutaneous injection or topical anesthetic to no anesthetic. METHODS: We conducted a retrospective review of 585 sequential ultrasound guided thyroid FNA procedures in Mayo Clinic. Group 1 (n = 200), no anesthetic; Group 2 (n = 185), subcutaneous injection anesthetic; and Group 3 (n = 200), topical anesthetic. Patient demographics, number of FNA passes, needle gauge, and cytopathology were recorded plus a discomfort score (0 to 10) before and immediately post procedure in all 3 groups and peak discomfort during the FNA in Groups 1 and 2. RESULTS: There were no differences among the 3 groups in age, sex, FNA sufficiency rate, cytopathology, and FNA passes number. There was no significant difference between Groups 1 and 2 in peak discomfort score during the FNA: 0 (45%, 42.2%), 1 to 2 (19%, 24.9%), 3 to 5 (23.5%, 20.5%), 6 to 8 (9.5%, 10.8%), 9 to 10 (3%, 1.6%), respectively. Discomfort score post procedure: 0 (78.5%, 77.8%, 53.5%), 1 to 2 (13%, 13%, 36.5%), 3 to 5 (7%, 7%, 9%), 6 to 8 (1.5%, 2.2%, 1%), 9 to 10 (0%, 0%, 0%) for groups 1, 2, and 3, respectively. There were no significant differences among the 3 groups for a discomfort score ≥3. CONCLUSION: FNA associated patient discomfort was comparable during and after the procedure regardless of the use of anesthetic or the type utilized. Approximately 90% of patients experienced mild to moderate discomfort during the procedure. And 90% reported no more than a level 2 discomfort post procedure. ABBREVIATIONS: End = endocrinology; FNA = fine-needle aspiration; MCF = Mayo Clinic Florida; MCR = Mayo Clinic Rochester.

Association of Thyrotropin Suppression With Survival Outcomes in Patients With Intermediate- and High-Risk Differentiated Thyroid Cancer.

Importance: Suppression of thyrotropin (often referred to as thyroid-stimulating hormone, or TSH) with levothyroxine used in management of intermediate- and high-risk differentiated thyroid cancer (DTC) to reduce the likelihood of progression and death is based on conflicting evidence. Objective: To examine a cohort of patients with intermediate- and high-risk DTC to assess the association of thyrotropin suppression with progression-free survival (PFS) and overall survival. Design, Setting, and Participants: This cohort study used a multicenter database analysis including patients from tertiary referral centers and local clinics followed up for a mean (SD) of 7.2 (5.8) years. Patients with DTC treated uniformly with total thyroidectomy and radioactive iodine between January 1, 1979, and March 1, 2015, were included. Among the 1012 patients, 145 patients were excluded due to the lack of longitudinal thyrotropin measurements. Exposures: Levothyroxine therapy to target thyrotropin suppression with dose adjustments based on changing thyrotropin goal. Main Outcomes and Measures: The primary outcome measures were overall survival and PFS. A Cox proportional hazards model was used to assess the contribution of age, sex, tumor size, histology, and lymph node and distant metastases at landmarks 1.5, 3.0, and 5.0 years. The patients were divided into 3 groups based on mean thyrotropin score before each landmark: (1) suppressed thyrotropin, (2) moderately suppressed or low-normal thyrotropin, and (3) low-normal or elevated thyrotropin. Results: Among 867 patients (557 [64.2%] female; mean [SD] age, 48.5 [16.5] years) treated with a median (range) cumulative dose of 151 (30-1600) mCi radioactive iodine, disease progression was observed in 293 patients (33.8%), and 34 patients (3.9%) died; thus, the study was underpowered in death events. Thyrotropin suppression was not associated with improved PFS at landmarks 1.5 (P = .41), 3.0 (P = .51), and 5.0 (P = .64) years. At 1.5 and 3.0 years, older age (hazard ratio [HR], 1.06; 95% CI, 1.03-1.08 and HR, 1.05; 95% CI, 1.01-1.08, respectively), lateral neck lymph node metastases (HR, 4.64; 95% CI, 2.00-10.70 and HR, 4.02; 95% CI, 1.56-10.40, respectively), and distant metastases (HR, 7.54; 95% CI, 3.46-16.50 and HR, 7.10; 95% CI, 2.77-18.20, respectively) were independently associated with subsequent time to progression, while at 5.0 years, PFS was shorter for patients with lateral neck lymph node metastases (HR, 3.70; 95% CI, 1.16-11.90) and poorly differentiated histology (HR, 71.80; 95% CI, 9.80-526.00). Conclusions and Relevance: Patients with intermediate- and high-risk DTC might not benefit from thyrotropin suppression. This study provides the justification for a randomized trial.

ThyroSeq®V2.0 Molecular Testing: A Cost-Effective Approach for the Evaluation of Indeterminate Thyroid Nodules.

OBJECTIVE: Approximately 15 to 30% of thyroid nodules have indeterminate cytology. Many of these nodules are treated surgically, but only 5 to 30% are malignant. Molecular testing can further narrow the risk of malignancy of these nodules. Our objective was to assess the cost effectiveness of ThyroSeq®V2.0 compared to diagnostic thyroidectomy for the evaluation of indeterminate nodules. METHODS: Cytology and histopathology slides of Bethesda category III and IV (suspicious for follicular neoplasia [SFN]) nodules obtained between January 1, 2014 and November 30, 2016 were re-reviewed by 2 endocrine cytopathologists. Costs for a diagnostic approach using ThyroSeq® were calculated and compared to those of diagnostic thyroidectomy. RESULTS: We included 8 Bethesda category III nodules that underwent ThyroSeq® and 8 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 4 were positive for mutations and underwent thyroid surgery. The average cost per nodule evaluated was $14,669 using ThyroSeq®, compared to $23,338 for diagnostic thyroid surgery. The cost per thyroid cancer case detected was $58,674 using ThyroSeq® compared to $62,233 for diagnostic thyroid surgery. We included 13 nodules Bethesda category IV that underwent ThyroSeq® and 11 that underwent diagnostic surgery. Of those submitted for ThyroSeq®, 6 were positive for mutation and underwent thyroid surgery. The average costs per nodule evaluated were $14,641 using ThyroSeq® and $24,345 using diagnostic thyroidectomy. The cost per thyroid cancer case detected was $31,721 when using ThyroSeq® compared to $53,560 for diagnostic thyroidectomy. CONCLUSION: The use of ThyroSeq® in our institution is cost effective compared to diagnostic thyroid surgery for the evaluation of Bethesda categories III and IV (SFN) nodules. ABBREVIATIONS: FNA = fine-needle aspiration; GEC = gene expression classifier; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; PTC = papillary thyroid cancer; SFN = suspicious for follicular neoplasia.

Over-the-Counter "Adrenal Support" Supplements Contain Thyroid and Steroid-Based Adrenal Hormones.

OBJECTIVE: To assess whether dietary supplements that are herbal and/or animal-derived products, marketed for enhancing metabolism or promoting energy, "adrenal fatigue," or "adrenal support," contain thyroid or steroid hormones. METHODS: Twelve dietary adrenal support supplements were purchased. Pregnenolone, androstenedione, 17-hydroxyprogesterone, cortisol, cortisone, dehydroepiandrosterone sulfate, synthetic glucocorticoids (betamethasone, dexamethasone, fludrocortisone, megestrol acetate, methylprednisolone, prednisolone, prednisone, budesonide, and triamcinolone acetonide) levels were measured twice in samples in a blinded fashion. This study was conducted between February 1, 2016, and November 1, 2016. RESULTS: Among steroids, pregnenolone was the most common hormone in the samples. Budesonide, 17-hydroxyprogesterone, androstenedione, cortisol, and cortisone were the others in order of prevalence. All the supplements revealed a detectable amount of triiodothyronine (T3) (63-394.9 ng/tablet), 42% contained pregnenolone (66.12-205.2 ng/tablet), 25% contained budesonide (119.5-610 ng/tablet), 17% contained androstenedione (1.27-7.25 ng/tablet), 8% contained 17-OH progesterone (30.09 ng/tablet), 8% contained cortisone (79.66 ng/tablet), and 8% contained cortisol (138.5 ng/tablet). Per label recommended doses daily exposure was up to 1322 ng for T3, 1231.2 ng for pregnenolone, 1276.4 ng for budesonide, 29 ng for androstenedione, 60.18 ng for 17-OH progesterone, 277 ng for cortisol, and 159.32 ng for cortisone. CONCLUSION: All the supplements studied contained a small amount of thyroid hormone and most contained at least 1 steroid hormone. This is the first study that measured thyroid and steroid hormones in over-the-counter dietary "adrenal support" supplements in the United States. These results may highlight potential risks of hidden ingredients in unregulated supplements.

Symptomatic Ovarian Steroid Cell Tumor not Otherwise Specified in a Post-Menopausal Woman.

Steroid cell tumor not otherwise specified (NOS) is a rare subtype of sex cord stromal tumor of the ovary and contributes less than 0.1% of all ovarian neoplasms. The majority of tumors occur in pre-menopausal women (mean age: 43 years), in which 56-77% of patients present with virilization due to excess testosterone. An 80-year-old woman with worsening alopecia and excessive growth of coarse hair on abdomen and genital area was found to have elevated serum testosterone level (462 ng/mL). Radiologic studies were consistent with bilateral adrenal adenomas. Bilateral adrenal venous sampling ruled out the adrenal gland as origin of hormone secretion. A diagnostic and therapeutic bilateral salpingo-oophorectomy confirmed steroid cell tumor NOS of the left ovary. Post-operatively, the patient had complete resolution of her symptoms and normalization of testosterone level. Our case emphasizes the importance of a clinical suspicion for an occult testosterone secreting ovarian tumor in a symptomatic patient without obvious ovarian mass on imaging.

MEN1 mutations in Hürthle cell (oncocytic) thyroid carcinoma.

CONTEXT AND OBJECTIVE: Oncocytic thyroid carcinoma, also known as Hürthle cell thyroid carcinoma, accounts for only a small percentage of all thyroid cancers. However, this malignancy often presents at an advanced stage and poses unique challenges to patients and clinicians. Surgical resection of the tumor accompanied in some cases by radioactive iodine treatment, radiation, and chemotherapy are the established modes of therapy. Knowledge of the perturbed oncogenic pathways can provide better understanding of the mechanism of disease and thus opportunities for more effective clinical management. DESIGN AND PATIENTS: Initially, two oncocytic thyroid carcinomas and their matched normal tissues were profiled using whole genome sequencing. Subsequently, 72 oncocytic thyroid carcinomas, one cell line, and five Hürthle cell adenomas were examined by targeted sequencing for the presence of mutations in the multiple endocrine neoplasia I (MEN1) gene. RESULTS: Here we report the identification of MEN1 loss-of-function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma. Whole genome sequence data also revealed large regions of copy number variation encompassing nearly the entire genomes of these tumors. CONCLUSION: Menin, a ubiquitously expressed nuclear protein, is a well-characterized tumor suppressor whose loss is the cause of MEN1 syndrome. Menin is involved in several major cellular pathways such as regulation of transcription, control of cell cycle, apoptosis, and DNA damage repair pathways. Mutations of this gene in a subset of Hürthle cell tumors point to a potential role for this protein and its associated pathways in thyroid tumorigenesis.

Clinical and molecular features of Hürthle cell carcinoma of the thyroid.

CONTEXT: Hürthle cell cancer (HCC) of the thyroid remains the subject of controversy with respect to natural course, treatment, and follow-up. OBJECTIVE: The objective of the study was to evaluate the clinical and molecular features associated with outcome in HCC. DESIGN: The study was a review of 173 HCC cases treated at Mayo Clinic over 11 years with a median 5.8-year follow-up. RESULTS: None of the patients with minimally invasive histology had persistent disease, clinical recurrence, or disease-related death. Male gender and TNM stage were independently associated with increased risk of clinical recurrence or death in widely invasive patients. The 5-year cumulative probability of clinical recurrence or death was higher in patients with TNM stage III-IV (females, 74%; males, 91%) compared with patients with TNM stage I-II (females, 0%; males, 17%). Pulmonary metastases were best identified by computed tomography, whereas radioactive iodine scans were positive in only two of 27 cases. Thyroglobulin was detectable in patients with clinical disease, with the notable exception of five patients with distant metastases. The common TERT C228T promoter mutation was detected in both widely invasive and minimally invasive tumors. TERT mRNA was below the limit of detection in all samples. CONCLUSION: Widely invasive HCC with TNM stage III-IV is aggressive, with low probability of recurrence-free survival. Males have worse outcomes than females. Minimally invasive HCC appears to be considerably less aggressive. Radioactive iodine scan performs poorly in detecting distant disease. Although the TERT gene is mutated in HCC, the role of this mutation remains to be demonstrated.

RNA sequencing identifies multiple fusion transcripts, differentially expressed genes, and reduced expression of immune function genes in BRAF (V600E) mutant vs BRAF wild-type papillary thyroid carcinoma.

CONTEXT: The BRAF V600E mutation (BRAF-MUT) confers an aggressive phenotype in papillary thyroid carcinoma, but unidentified additional genomic abnormalities may be required for full phenotypic expression. OBJECTIVE: RNA sequencing (RNA-Seq) was performed to identify genes differentially expressed between BRAF-MUT and BRAF wild-type (BRAF-WT) tumors and to correlate changes to patient clinical status. DESIGN: BRAF-MUT and BRAF-WT tumors were identified in patients with T1N0 and T2-3N1 tumors evaluated in a referral medical center. Gene expression levels were determined (RNA-Seq) and fusion transcripts were detected. Multiplexed capture/detection and digital counting of mRNA transcripts (nCounter, NanoString Technologies) validated RNA-Seq data for immune system-related genes. PATIENTS: BRAF-MUT patients included nine women, three men; nine were TNM stage I and three were stage III. Three (25%) had tumor infiltrating lymphocytes. BRAF-WT included five women, three men; all were stage I, and five (62.5%) had tumor infiltrating lymphocytes. RESULTS: RNA-Seq identified 560 of 13 085 genes differentially expressed between BRAF-MUT and BRAF-WT tumors. Approximately 10% of these genes were related to MetaCore immune function pathways; 51 were underexpressed in BRAF-MUT tumors, whereas 4 (HLAG, CXCL14, TIMP1, IL1RAP) were overexpressed. The four most differentially overexpressed immune genes in BRAF-WT tumors (IL1B; CCL19; CCL21; CXCR4) correlated with lymphocyte infiltration. nCounter confirmed the RNA-Seq expression level data. Eleven different high-confidence fusion transcripts were detected (four interchromosomal; seven intrachromosomal) in 13 of 20 tumors. All in-frame fusions were validated by RT-PCR. CONCLUSION: BRAF-MUT papillary thyroid cancers have reduced expression of immune/inflammatory response genes compared with BRAF-WT tumors and correlate with lymphocyte infiltration. In contrast, HLA-G and CXCL14 are overexpressed in BRAF-MUT tumors. Sixty-five percent of tumors had between one and three fusion transcripts. Functional studies will be required to determine the potential role of these newly identified genomic abnormalities in contributing to the aggressiveness of BRAF-MUT and BRAF-WT tumors.

[Correlation between fever and the clinical severity of acute bronchiolitis]. / Corelatia dintre febra si severitatea clinica a bronsiolitei acute.

INTRODUCTION: The relationship between fever and the severity of acute infant bronchiolitis has been little studied, and the results of the few published studies are not concordant. AIM: To assess the significance of fever in children aged under 1 year with acute bronchiolitis. MATERIAL: 83 children aged between 0-1 year; hospitalized with the diagnosis of acute bronchiolitis during the winter of 2004-2005, assigned to two groups, with febrile bronchiolitis and afebrile bronchiolitis, respectively. METHOD: The evaluation of patients using a clinical score including respiratory effort, O2 saturation, respiratory rate, and the statistical processing of results comparatively in the two study groups. RESULTS: The mean duration of hospitalization was 5.8 days for febrile patients compared to 4.4 days for afebrile patients (p = 0.003). Infants with febrile bronchiolitis had a more severe clinical picture, evaluated by the clinical score, compared to afebrile patients (p = 0.03). CONCLUSION: Fever associated with acute bronchiolitis in children aged 0-1 year has the significance of a higher clinical severity and prolonged evolution of the disease.