Graves' Disease Following COVID-19 Vaccination: A Population-based, Matched Case-control Study.

OBJECTIVE: Multiple cases and case series reported Graves' disease (GD) following coronavirus disease 2019 (COVID-19) vaccination. We aimed to determine whether COVID-19 vaccination was associated with the incidence of GD. METHODS: We analyzed data from Clalit Health Services, the largest healthcare organization in Israel, which insures 4.7 million patients. A population-based, matched, case-control study was performed. Cases were defined as adult patients diagnosed with GD between December 2020 and November 2022. Each case was matched with controls in a 1:2 ratio. Each control was assigned an index date, which was identical to that of their matched case, defined as the date of GD diagnosis. Time between vaccination date and the diagnosis of GD or index date was assessed. RESULTS: A total of 726 patients with GD were matched with 1452 controls. The study patients and controls have received similar proportions of the COVID-19 vaccine [at least 1 dose: 80% (581/726) vs 77.8% (1129/1452), P = .22, respectively]. In a univariate analysis, at least 1 dose of the COVID-19 vaccine was not associated with the incidence of GD [odds ratio 95% confidence interval: 1.15 (.92-1.43)]. The mean time between first COVID-19 vaccination and the diagnosis of GD for cases or index date for controls was not significantly different [275.69 days (SD 144.37) for cases compared to 275.45 days (SD 145.76) for controls]. CONCLUSION: Our study found no association between COVID-19 vaccination and the incidence of GD.

Safety of monovalent and bivalent BNT162b2 mRNA COVID-19 vaccine boosters in at-risk populations in Israel: a large-scale, retrospective, self-controlled case series study.

BACKGROUND: COVID-19 continues to be a major health threat, particularly among at-risk groups, including individuals aged 60 years or older and people with particular medical conditions. Nevertheless, the absence of sufficient vaccine safety information is one of the key contributors to vaccine refusal. We aimed to assess the short-term safety profile of the BNT162b2 mRNA COVID-19 vaccine booster doses. METHODS: In this self-controlled case series study, we used a database of members of the largest health-care organisation in Israel. We analysed the medical records of individuals at risk of COVID-19 complications who had received two doses of the monovalent BNT162b2 mRNA COVID-19 vaccine (tozinameran, Pfizer-BioNTech) as their primary course of vaccination and then also received BNT162b2 mRNA COVID-19 vaccine boosters between July 30, 2021, and Nov 28, 2022, as a monovalent first or second booster, or as a bivalent first, second, or third booster, or a combination of these. We included individuals who had active membership of the health-care organisation and who were alive (excluding COVID-19 deaths) throughout the entire study period. We excluded individuals who, during the study period, were either not active Clalit Health Services members or died of non-COVID-19 causes, and those who were infected with COVID-19 during the 7-day period after vaccination. Individuals' at-risk status was assessed on the day before the baseline period started. The primary outcome was non-COVID-19 hospitalisation for 29 adverse events that might be associated with vaccination. For each adverse event, we compared the risk difference of hospitalisation during a 28-day pre-vaccination baseline period versus during a 28-day post-vaccination period, using a non-parametric percentile bootstrap method. FINDINGS: Of the 3 574 243 members of the health-care organisation, 1 073 110 received a first monovalent booster, 394 251 received a second monovalent booster, and 123 084 received a bivalent first, second, or third booster. Overall, we found no indication of an elevated risk of non-COVID-19 hospitalisation following administration of any of the booster vaccines (risk difference in events per 100 000 individuals: first monovalent booster -37·1 [95% CI -49·8 to -24·2]; second monovalent booster -37·8 [-62·2 to -13·2]; and bivalent booster -18·7 [-53·6 to 15·4]). Except for extremely rare elevated risks after the first monovalent booster-of myocarditis (risk difference 0·7 events per 100 000 individuals [95% CI 0·3-1·3]), seizures (2·2 [0·4-4·1]), and thrombocytopenia (2·6 [0·7-4·7])-we found no safety signals in other adverse events, including ischaemic stroke. INTERPRETATION: This study provides the necessary vaccine safety assurances for at-risk populations to receive timed roll-out booster vaccinations. These assurances could reduce vaccine hesitancy and increase the number of at-risk individuals who opt to become vaccinated, and thereby prevent the severe outcomes associated with COVID-19. FUNDING: Israel Science Foundation and Israel Precision Medicine Partnership programme.

Risk assessment of human mpox infections: retrospective cohort study.

OBJECTIVES: The global supply of vaccines against mpox (previously called monkeypox virus infection) was significantly lower than the demand. Therefore, evidence-based vaccine prioritization criteria, based on risk assessment were needed. Our objective was therefore to identify the characteristics of individuals at the highest risk for mpox. METHODS: This population-based cohort study included all Clalit Health Services (CHS) subjects assumed to be at risk for mpox. The eligibility criteria for inclusion were determined based on known characteristics of people with infection worldwide and insights of lesbian, gay, bisexual, transgender, queer+ (LGBTQ+) -specialized CHS clinicians. Cox hazards models were used to identify the risk factors for mpox within the study cohort. The study commenced on 6 June 2022, the date of the first known mpox in CHS members, until 31 July 2022, when the mpox vaccination campaign started. RESULTS: A total of 8088 individuals of 4.7 million CHS members (0.18%) were identified according to the study inclusion criteria. Of those, 69 (0.85%) developed infection during the study period. Risk factors for mpox were birth in 1980 or later (hazard ratio, 5.04; 95% CI, 2.11-12.02), history of syphilis (2.62; 1.58-4.35), registration to primary healthcare clinics in the Tel Aviv district (2.82; 1.44-5.54), HIV-pre-exposure prophylaxis medication use (3.96; 2.14-7.31), PDE5 inhibitors use (2.92; 1.77-4.84), and recent sexually transmitted infections (STIs) within the last 18 months (2.27; 1.35-3.82). No infections were observed in individuals with none of the factors. Individuals with three or more risk factors had a 20.30-fold (10.39-39.69) higher risk for mpox compared with those with 0-2, with 85.5% (75.0-92.8%) sensitivity and 77.8% (76.9-78.7%) specificity. DISCUSSION: Weighting individuals' risk levels based on validated risk factors against vaccine availability can assist health systems in the equitable prioritization of vaccine allocation in various future outbreaks, given supply-demand gaps.

Effectiveness of a bivalent mRNA vaccine booster dose to prevent severe COVID-19 outcomes: a retrospective cohort study.

BACKGROUND: In late 2022, the SARS-CoV-2 omicron (B.1.1.529) BA.5 sublineage accounted for most of the sequenced viral genomes worldwide. Bivalent mRNA vaccines contain an ancestral SARS-CoV-2 strain component plus an updated component of the omicron BA.4 and BA.5 sublineages. Since September, 2022, a single bivalent mRNA vaccine booster dose has been recommended for adults who have completed a primary SARS-CoV-2 vaccination series and are at high risk of severe COVID-19. We aimed to evaluate the effectiveness of a bivalent mRNA vaccine booster dose to reduce hospitalisations and deaths due to COVID-19. METHODS: We did a retrospective, population-based, cohort study in Israel, using data from electronic medical records in Clalit Health Services (CHS). We included all members of CHS who were aged 65 years or older and eligible for a bivalent mRNA COVID-19 booster vaccination. We used hospital records to identify COVID-19-related hospitalisations and deaths. The primary endpoint was hospitalisation due to COVID-19, which we compared between participants who received a bivalent mRNA booster vaccination and those who did not. A Cox proportional hazards regression model with time-dependent covariates was used to estimate the association between the bivalent vaccine and hospitalisation due to COVID-19 while adjusting for demographic factors and coexisting illnesses. FINDINGS: Between Sept 27, 2022, and Jan 25, 2023, 569 519 eligible participants were identified. Of those, 134 215 (24%) participants received a bivalent mRNA booster vaccination during the study period. Hospitalisation due to COVID-19 occurred in 32 participants who received a bivalent mRNA booster vaccination and 541 who did not receive a bivalent booster vaccination (adjusted hazard ratio 0·28, 95% CI 0·19-0·40). The absolute risk reduction for hospitalisations due to COVID-19 in bivalent mRNA booster recipients versus non-recipients was 0·089% (95% CI 0·075-0·101), and the number needed to vaccinate to prevent one hospitalisation due to COVID-19 was 1118 people (95% CI 993-1341). INTERPRETATION: Participants who received a bivalent mRNA booster vaccine dose had lower rates of hospitalisation due to COVID-19 than participants who did not receive a bivalent booster vaccination, for up to 120 days after vaccination. These findings highlight the importance of bivalent mRNA booster vaccination in populations at high risk of severe COVID-19. Further studies with longer observation times are warranted. FUNDING: None.

Hemoglobin decline as a signal for hyperprolactinemia onset prior to prolactinoma diagnosis in hypogonadal men.

BACKGROUND: Men harboring prolactinomas frequently suffer from central hypogonadism with secondary anemia. They present insidious and nonspecific symptoms of hypogonadism, making it difficult to diagnose the disease and determine its duration. The result is a delay in diagnosis, which may have harmful hormonal and metabolic consequences. We hypothesized that a decrease in hemoglobin (HB) levels prior to prolactinoma diagnosis, may signal hyperprolactinemia onset and estimate disease duration. METHODS: We retrospectively evaluated the prediagnosis temporal trends in HB levels of 70 males with prolactinoma, diagnosed from January 2010 to July 2022. Men without hypogonadism, patients that received testosterone, and those with unrelated anemia were excluded. RESULTS: Sixty-one of seventy men (87%) with prolactinoma presented with hypogonadism, and forty men (57%) had HB levels ≤13.5 g/dL at diagnosis. We identified 25 patients with "informative" HB curves (mean age, 46.1±14.9 years; median prolactin, 952 ng/mL; median follow-up, 14.0 years), demonstrating an obvious prediagnosis HB decrease (greater than 1.0 g/dL), from a prediagnosis baseline HB of 14.4 ± 0.3 to 12.9 ± 0.5 g/dL at diagnosis. The median "low-HB duration" (from the first low HB measurement to hyperprolactinemia diagnosis) was 6.1 years (IQR, 3.3-8.8 years). In symptomatic patients, we identified a correlation between "low-HB duration" and patient-reported sexual dysfunction duration (n = 17, R = 0.502, p = 0.04). The "low-HB duration" was significantly longer than the reported sexual dysfunction duration (7.0 ± 4.5 vs. 2.9 ± 2.5 years, p = 0.01). CONCLUSIONS: In our cohort of men with prolactinomas and hypogonadism, we found a marked decrease in HB levels that preceded prolactinoma diagnosis by a median of 6.1 years, with a mean delay of 4.1 years between HB decrease and hypogonadal symptoms appearance. These results suggest that HB decline prior to prolactinoma diagnosis may serve as a marker for hyperprolactinemia onset in a subset of hypogonadal men and allow a more accurate assessment of disease duration.

Natural history of nonfunctioning pituitary macroadenomas followed without intervention: A retrospective cohort study.

OBJECTIVE: The treatment strategy for nonfunctioning pituitary adenomas (NFPA) includes surgery, radiotherapy, medical treatment, or follow-up. Prior series of patients with NFPAs followed without intervention include small numbers of patients with macroadenomas. This study investigated the natural history of patients with macroadenomas followed without treatment. DESIGN AND PATIENTS: Retrospective cohort study included patients>18 years, with a diagnosis of NFPA ≥ 10 mm who were naïve to surgery or medical treatment and followed more than 12 months after diagnosis. Patients with chiasmal threat were excluded. Follow-up terminated if the patient underwent surgery, received cabergoline or was lost to follow-up. MEASUREMENTS: Data collected included evaluation of tumour characteristics and size by MRI, symptoms including visual disturbances, and hormonal levels. Tumour growth was defined as maximal diameter increase of ≥2 mm. RESULTS: The cohort included 49 patients (30 males, mean age 68.0 ± 12.0 years). At diagnosis, the average tumour size was 17.8 ± 5.9 mm. Mean follow-up time was 4.9 ± 4.9 years. Increase in tumour size occurred in 16 patients (33%), with an average growth of 5.1 ± 4.4 mm. Reduction in tumour size occurred in 10 patients (20%), with a mean decrease of 3.5 ± 1.3 mm. Twenty-three patients remained with stable tumours. Overall, 33 patients (67%) were observed without any intervention; 3 patients were operated and 13 were treated with cabergoline. None of the parameters including age, gender, baseline tumour size, invasiveness, visual disturbances, or hypopituitarism at diagnosis, predicted tumour growth. CONCLUSION: Observation of NFPAs without surgery or medical therapy is a reasonable approach in selected patients. In our study, no parameter predicted tumour growth.

Real-world effectiveness of a single dose of mpox vaccine in males.

The recent global outbreak of the monkeypox (mpox) virus in humans was declared a public health emergency by the World Health Organization in July 2022. The smallpox and mpox vaccine (JYNNEOS; Modified Vaccinia Ankara-Bavarian Nordic; MVA-BN), provided as a two-dose regimen, is currently the primary vaccine utilized against mpox. However, the efficacy of MVA-BN against mpox has never been demonstrated in clinical trials to date. Due to the limited supply of vaccines, the World Health Organization has recommended prioritizing the vaccination of high-risk groups. We evaluated the real-world effectiveness of a single, subcutaneous dose of MVA-BN in this observational, retrospective cohort study, which included the analysis of electronic health records of all members of Clalit Health Services eligible for the vaccine on 31 July 2022. We used a Cox proportional hazards regression model with time-dependent covariates to estimate the association between vaccination and mpox while adjusting for sociodemographic and clinical risk factors. In an analysis of 2,054 male individuals who met vaccine eligibility criteria, 1,037 (50%) were vaccinated during the study recruitment period and completed at least 90 d of follow-up. During the study period, 5 and 16 infections were confirmed in vaccinated and unvaccinated individuals, respectively. The adjusted vaccine effectiveness was estimated at 86% (95% confidence interval, 59-95%). Our results suggest that a single dose of subcutaneous MVA-BN in this high-risk cohort is associated with a significantly lower risk of MPXV infection.

Predicting hypogonadotropic hypogonadism persistence in male macroprolactinoma.

PURPOSE: To study the baseline characteristics predicting hypogonadotropic hypogonadism (HH) persistence in men with macroprolactinoma that achieved prolactin normalization. DESIGN: Retrospective cohort study. METHODS: Male patients diagnosed with macroprolactinoma and HH that received cabergoline treatment with subsequent prolactin normalization were included: men that achieved eugonadism, and men that remained hypogonadal. Patient's demographic, clinical and biochemical parameters, sellar imaging, and visual fields tests were obtained. Univariate and multivariate models were used to identify predictors of HH persistence. RESULTS: Fifty-eight male patients (age 49.2 ± 12.6 years) with a median baseline prolactin of 1154 ng/mL (IQR 478-2763 ng/mL) and adenoma (maximal) diameter of 25.9 ± 14.8 mm were followed for a median of 5.6 years (IQR 3.0-10.7). Twelve men (21%) suffered from HH persistence at the end of follow-up and 46 men achieved eugonadism. Forty-two out of 46 men (91%) accomplished eugonadism within the first year following prolactin normalization. In a multivariate logistic regression model, hypopituitarism (OR 10.1; 95% CI 1.10-101.94), visual field defect (OR 9.9; 95% CI 1.07-92.33), and low baseline testosterone levels (OR 0.5; 95% CI 0.29-0.93) were independent predictors of HH persistence. CONCLUSION: In our cohort of men with macroprolactinoma that reached prolactin normalization with cabergoline treatment, 21% had HH persistence. Pituitary hormone deficiency, visual field defects, and low baseline testosterone levels were independently associated with HH persistence. 91% of men achieved eugonadism within the first year following prolactin normalization. These findings may support informed clinical decision-making regarding the initiation of testosterone replacement in men with macroprolactinomas.

Subclinical acromegaly: to treat or not to treat?

Patients with acromegaly usually present with the classical signs of acromegaly, whereas patients without the specific signs or symptoms are rarely diagnosed. This unique entity can be named "subclinical acromegaly". This was a retrospective study. Our study group consisted of 6 patients (4 females) with incidentally diagnosed acromegaly, most following head MRI for unrelated reasons and without the specific signs of acromegaly. Mean age at diagnosis was 48.8 ± 19.2 years. Baseline IGF-1 ranged between 1.3-2.0 × upper limit of normal (ULN). MRI depicted a pituitary microadenoma in 5 patients, and one patient presented with a 12 mm intra-sellar macroadenoma. Mean calculated SAGIT clinical score was 4.8. Three patients underwent trans-sphenoidal resection; two achieved hormonal remission and one improved but did not normalize IGF-1 following surgery. Four patients (including one following surgery) were given somatostatin analogs, and three normalized IGF-1. Several patients improved clinically following treatment, reporting improvement in snoring, hypertension, or weight loss, and pituitary adenoma decreased in size in 2 patients that responded to medical treatment. We report a series of 6 patients with very mild and subclinical acromegaly. It is uncertain whether all such patients will gain clinical benefit from treatment, but most experienced clinical improvement due to treatment.

Polymicrobial and monomicrobial necrotizing soft tissue infections: comparison of clinical, laboratory, radiological, and pathological hallmarks and prognosis. A retrospective analysis.

BACKGROUND: Necrotizing soft tissue infection (NSTI) is a life-threatening infection associated with high morbidity and mortality. Treatment consists of surgery and antibiotics. Many studies have addressed NSTI and its subtypes, but few have reviewed the clinical, radiological, and pathological differences between the polymicrobial and monomicrobial diseases. The objective of our study was to evaluate the clinical, radiological, and pathological features of patients with polymicrobial (NSTI I) and monomicrobial (NSTI II) infections and their association with outcome. METHODS: The cohort consisted of patients hospitalized with NSTI at a tertiary medical center in 2002-2019. The medical charts were reviewed for clinical, radiological, and pathological features. Findings were compared between patients in whom blood/tissue bacterial cultures yielded one or more than one pathological isolate. The primary clinical outcome measure of the study was all-cause mortality at 90 days. Secondary outcomes were duration of hospitalization, intensive care unit (ICU) admission, score on the LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis), and need for vasopressor treatment. RESULTS: A total of 81 patients met the inclusion criteria: 54 (66.6%) with monomicrobial NSTI and 27 (33.3%) with polymicrobial NSTI. There were no significant between-group differences in in-hospital and 90-day mortality. On multivariate analysis, the monomicrobial disease group had a significantly higher 90-day mortality rate in addition to higher rates of in-hospital mortality, ICU admission, and vasopressor use than the polymicrobial disease group. CONCLUSION: Our study is the first to compare the clinical, radiological, and pathological differences between the two most common types of NSTI. The results demonstrate better prognosis for polymicrobial NSTI, with minimal ICU stay, lower mortality, and lower use of vasopressors. LEVEL OF EVIDENCE: Prognostic and epidemiological, level III.

Long-term response to cabergoline and multi-modal treatment in men with macroprolactinoma: Does size really matter?

OBJECTIVE: To study the outcome of men with macroprolactinoma following cabergoline treatment based on tumour size. DESIGN: Retrospective cohort study. METHODS: The study included 94 men, divided into three groups according to adenoma diameter: 10-19 mm (Group A, n = 36); 20-39 mm (Group B, n = 41); or ≥40 mm (Group C, giant prolactinomas, n = 17). Patients were followed for a mean of 7.5 years with sellar magnetic resonance imaging, visual fields and hormone measurements. RESULTS: Mean baseline prolactin was 767, 2090 and 24,806 ng/ml in Groups A, B and C, respectively (p < .01). Prolactin suppression below three times the upper limit of normal (ULN) was achieved in 34 (94%; mean weekly cabergoline dose of 1.2 mg), 37 (90%; cabergoline dose, 2.1 mg) and 15 (88%; cabergoline dose, 2.8 mg) men (p = .31) in each group. After excluding patients who underwent surgery and radiotherapy, cabergoline suppressed prolactin below three times ULN in 32/35 (91%), 29/37 (78%) and 11/14 (79%) men in Groups A, B and C, respectively (p = .27). Visual deficits were observed in 5 (14%), 12 (29%) and 10 (59%) patients (p < .01); improvement was achieved in 5/5 (100%), 11/12 (92%) and 10/10 (100%) of men in Groups A, B and C. Low baseline testosterone was measured in 26 (72%), 39 (95%) and 17 (100%) patients in the three groups (p < .01). Following multi-modal treatment, hypogonadism persisted in 3 (8%), 5 (12%) and 2 (12%) men, respectively (p = .85). CONCLUSION: Macroprolactinomas in men were controlled with cabergoline in 84% of cases, independent of tumour size. Pituitary surgery and adjuvant radiotherapy further improved long-term response to 91%.

True hyperprolactinemia in men without visible pituitary adenoma.

PURPOSE: Men with mild to moderate hyperprolactinemia rarely present with normal pituitary on MRI with no visible adenoma, a condition entitled also "idiopathic hyperprolactinemia" or "non-tumoral hyperprolactinemia". We have characterized a cohort of hyperprolactinemic men with normal pituitary imaging. DESIGN: We have identified 13 men with true hyperprolactinemia and normal pituitary MRI. Baseline clinical and hormonal characteristics and response to medical treatment were retrospectively retrieved from medical records. RESULTS: Mean age at diagnosis was 51 ± 16 years (range, 20-77); mean serum prolactin level at presentation was 91 ng/ml (range, 28-264), eight men presented with low baseline testosterone. Initial complaints leading to diagnosis included sexual dysfunction in ten men and gynecomastia in five. All patients were treated with cabergoline, except for one who was given bromocriptine; none required pituitary surgery. All patients normalized prolactin and testosterone with subsequent clinical improvement reported by most men. Currently, after a mean follow-up of 72 months, ten patients continue treatment with caborgoline (median weekly dose, 0.25 mg), whereas three men discontinued treatment. CONCLUSIONS: Men with symptomatic hyperprolactinemia may rarely present with normal pituitary imaging. Medical treatment can lead to hormonal improvement with clinical benefit.

Benefits of a nurse-led home injection service for acromegaly patients treated with somatuline autogel.

AIM: The aim of this study is to assess the benefits of a nurse-led home injection service for somatuline autogel-treated patients with acromegaly, including the adherence to treatment and disease control. METHODS: Historical prospective data of all patients with acromegaly initiating somatuline autogel between November 14, 2000, and March 9, 2020, who voluntarily enrolled in the nurse-led home injection service between January 1, 2018 and June 30, 2020. Adherence to treatment was calculated as the number of administered injections divided by the number of expected injections during the follow-up period. Excellent adherence to treatment was defined when >90% of scheduled injections were administered, while low adherence was defined when patients received <80% of expected injections. The primary outcome was the adherence to treatment. RESULTS: The cohort included 88 patients (mean age ± SD, 59.8 ± 14.9 years, 53% men). Average adherence to treatment was 93 ± 8% (range 62-100%). Excellent adherence was documented in 65 participants (74%), of which 29 patients (33%) received all scheduled injections. Low adherence to treatment was recorded in seven patients (8%). Average adherence was high independent of gender, age, prior surgery, or radiation therapy, or whether somatuline autogel was used as monotherapy or in combination regimens. However, excellent adherence decreased with increased somatuline dose and with dosing interval of 21 days. Average adherence was slightly higher in patients with biochemically controlled acromegaly. CONCLUSIONS: A nurse-led home injection service for somatuline autogel injections is associated with high adherence to treatment. Establishing such a program globally may lead to better adherence to treatment and improved disease control.

Hyperparathyroidism in patients over 75: Clinical characteristics and outcome. Is conservative treatment a safe alternative?

OBJECTIVE: With the current aging of the world's population, primary hyperparathyroidism (PHPT) is increasingly detected in the elderly. Yet data on the presentation and outcome of PHPT in this group are scarce. The objective was to describe a cohort of patients aged 75 years or more with PHPT observed in our endocrine clinic. STUDY DESIGN: A retrospective analysis of medical records in an endocrine clinic at a tertiary hospital. We evaluated 182 patients with PHPT, aged 75 years or more at their last follow-up, all diagnosed at age 65 or more. Laboratory data were compared at diagnosis and last follow-up. RESULTS: Mean age at diagnosis was 73 ± 4 years, last follow-up was at 83 ± 4 years, and mean follow-up was 11.3 ± 5.5 years. Osteoporosis, fractures, and nephrolithiasis were diagnosed in 114(63 %), 84(46 %), and 43(24 %) patients, respectively. Overall, 150 patients had an indication for surgery; of them, the 29 who underwent parathyroidectomy were younger than the non-operated patients and had higher rates of hypercalciuria. During the follow-up of the 141 patients who did not undergo operation, serum and urinary calcium levels significantly had decreased, and vitamin D level had increased at last visit (10.4 ± 0.5 mg/dl, 161 ± 70 mg/24 h, 69 ± 17 nmol/l, p < 0.01 respectively) compared with levels at diagnosis (10.6 ± 0.2 mg/dl, 223 ± 95 mg/24 h, 53 ± 15 nmol/l, respectively, p = 0.001). Overall, 38 of the 182 patients (20 %) died during follow-up; these patients were significantly older at diagnosis (76 ± 5 vs. 72 ± 4 years) but there were no differences in laboratory variables. CONCLUSIONS: While most patients had a formal indication for surgery, few underwent parathyroidectomy. Serum and urinary calcium significantly decreased during follow-up in patients who did not undergo surgery. Our data are reassuring and support at least the consideration of conservative treatment for these patients.

Detecting Recurrence Following Lobectomy for Thyroid Cancer: Role of Thyroglobulin and Thyroglobulin Antibodies.

BACKGROUND: The use of thyroglobulin (Tg) and thyroglobulin antibodies (TgAb) for detecting disease recurrence is well validated following total thyroidectomy and radioiodine ablation. However, limited data are available for patients treated with thyroid lobectomy. METHODS: Patients who had lobectomy for papillary thyroid cancer followed for >1 year, with sufficient data on Tg and TgAb, including subgroup analysis for Hashimoto's thyroiditis and contralateral nodules. RESULTS: One-hundred sixty-seven patients met the inclusion criteria. Average tumor size was 9.5 ±â€…6 mm. Following lobectomy, Tg was 12.1 ±â€…14.8 ng/mL. Of 52 patients with Hashimoto's thyroiditis, 38% had positive TgAb with titers of 438 ±â€…528 IU/mL, and in patients without TgAb the mean Tg level was 14.7 ±â€…19.0 ng/mL. In 34 patients with contralateral nodules ≥1 cm, Tg was 15.3 ±â€…17 ng/mL. During the first 2 years of follow-up, Tg declined ≥1 ng/mL in 42% of patients (by 5.1 ±â€…3.7 ng/mL), remained stable in 22%, and increased in 36% (by 4.9 ±â€…5.7 ng/mL). During a mean follow-up of 6.5 years (78 ±â€…43.5 months), 18 patients had completion thyroidectomy and 12 were diagnosed with contralateral cancer (n = 8) or lymph node metastases (n = 4). In patients with recurrence followed for >2 years, there was a rise in Tg in 3 cases, Tg was stable in 2 cases, and in 1 TgAb decreased from 1534 to 276 IU/mL despite metastatic lymph nodes. Basal Tg and Tg dynamics did not predict disease recurrence. CONCLUSIONS: Serum thyroglobulin used independently is of limited value for predicting or detecting disease recurrence following thyroid lobectomy. Other potential roles of Tg, such as detecting distant metastases following lobectomy, should be further studied.

Response to Therapy Assessment in Intermediate-Risk Thyroid Cancer Patients: Is Thyroglobulin Stimulation Required?

Introduction: The 2015 American Thyroid Association (ATA) guidelines recommend response to therapy (RTT) assessment 1-2 years after initial treatment in differentiated thyroid cancer (DTC) patients to guide thyrotropin (TSH) goals and long-term follow-up. We hypothesized that data collected during the first 2 years of follow-up may be sufficient to determine RTT without thyroglobulin (Tg) stimulation. Materials and Methods: Patients treated with total thyroidectomy and radioiodine for intermediate-risk DTC, followed for >2 years, and had sufficient follow-up data were included. Data on Tg, ultrasound, scans, and long-term outcomes were collected. Results: One-hundred twenty patients met inclusion criteria, with 68% women and mean age 55 ± 15 years. Intermediate risk was due to lymph-node involvement (72%), extrathyroidal extension (51%), vascular invasion (12%), and high-risk histology (9%). At the end of follow-up of 7 ± 4 years, 26% had persistent disease (14% biochemical, 12% structural). According to the ATA RTT system (using stimulated-Tg), 56% had excellent RTT, of whom only 2% had disease at the end of follow-up. In the "nonstimulated" system (which includes basal Tg, post-131I therapy whole-body scan (TxWBS) for assessment of residual lymph-node metastases after surgery, and structural imaging studies), 57% had excellent response, of whom none had disease at the end of follow-up. Only eight patients (7%) were classified differently due to recombinant human thyrotropin stimulation (as either excellent or indeterminate response), with no difference in predictive value, with a receiver-operator characteristic area under the curve of 0.903 with Tg-stimulation and of 0.918 without. Conclusions: In patients with no evidence of disease during the first 2 years of follow-up, the addition of stimulated-Tg adds little prognostic information. We suggest the use of excellent RTT based on basal Tg together with TxWBS and structural imaging studies.

Prolactinomas in males: any differences?

CONTEXT: Prolactinomas in men are usually large and invasive, presenting with signs and symptoms of hypogonadism and mass effects, including visual damage. Prolactin levels are high, associated with low testosterone, anemia, metabolic syndrome and if long-standing also osteoporosis. RESULTS: Medical treatment with the dopamine agonist, cabergoline, became the preferred first-line treatment for male prolactinomas as well as for giant tumors, leading to prolactin normalization in ~ 80% of treated men, and tumor shrinkage, improved visual fields and recovery of hypogonadism in most patients. Multi-modal approach including surgery and occasionally radiotherapy together with a high-dose cabergoline is saved for resistant and invasive adenomas. Experimental treatments including temozolomide or pasireotide may improve clinical response in men harboring resistant prolactinomas. CONCLUSIONS: Compared to other pituitary adenomas, secreting and non-secreting, where pituitary surgery is the recommended first-line treatment, men with prolactinomas will usually respond to medical treatment with no need for any additional treatment.

Bone-Marrow Suppression in Elderly Patients Following Empiric Radioiodine Therapy: Real-Life Data.

Background: Elderly patients with differentiated thyroid cancer (DTC) tend to have more advanced disease at presentation, for which high activities of radioiodine (RAI) are often recommended. However, the 2015 American Thyroid Association guidelines recommend that empirically administered activities of RAI >150 mCi should be avoided in patients >70 years of age, based on calculated bone-marrow exposure according to two dosimetry-based studies. This study aimed to evaluate the effect of RAI treatment on bone-marrow function in elderly DTC patients. Methods: DTC patients ≥70 years of age who received RAI treatment and on whom a complete blood count was performed before and after treatment were included. Blood counts within one year before RAI and one year following treatment were compared in order to assess for marrow suppression. The impact of demographic, clinical, and laboratory variables on complete blood count were assessed. Results: One hundred fifty-three treatments in 122 patients met inclusion criteria, with a mean patient age of 76 ± 4.3 years, and 75% were women. High-risk features at presentation included T4 disease in 17%, lymph node metastases in 34%, and distant metastases in 14%. Mean RAI activity was 136.8 ± 48 mCi (82% ≥ 100 mCi, 66% ≥ 150 mCi). Of 153 RAI treatments analyzed, 114 (74%) were first treatments, 28 (18%) second treatments, seven (5%) third treatments, and four (3%) fourth treatments. At 0-3 months after RAI treatment, there was a statistically significant decrease in platelets (238 ± 66 vs. 216 ± 69 × 109/L, 10% decrease; p < 0.001), white blood cells (WBC; 6.9 ± 2 vs. 6.1 ± 1.9 × 109/L, 13% decrease; p < 0.001), and hemoglobin (Hb) in women (12.8 ± 1.1 vs. 12.4 ± 1.1 g/dL, 3% decrease; p = 0.01). Mean platelets, WBC, Hb in women, and lymphocytes remained decreased (but within the reference range) one year after treatment. Subgroup analysis demonstrated platelet suppression only with activities ≥100 mCi, and WBC and Hb suppression only with activities ≥150 mCi, with mean values within the reference ranges. There were no clinically significant cytopenia events during follow-up. Conclusions: Empiric RAI treatment in elderly patients causes mild bone-marrow suppression, with little clinical significance. Activities of 150-200 mCi can be safely used when indicated.

DISEASE PRESENTATION AND REMISSION RATE IN GRAVES DISEASE TREATED WITH ANTITHYROID DRUGS: IS GENDER REALLY A FACTOR?

OBJECTIVE: Male gender is considered an adverse prognostic factor for remission of Graves disease treatment with antithyroid drugs (ATDs), although published data are conflicting. This often results in early consideration of radioiodine treatment and surgery for men. Our objective was to compare disease presentation and outcome in men versus women treated with ATDs. METHODS: Retrospective study of 235 patients (64 men, 171 women) with Graves disease who were evaluated for features at presentation and outcome at the end of follow-up between 2010 and 2015. RESULTS: Disease presentation was similar in men and women for age at diagnosis (41.4 ± 14 years vs. 40 ± 15 years), duration of follow-up (6.6 ± 7 years vs. 7.7 ± 6 years), rates of comorbid autoimmune diseases, and rate of Graves ophthalmopathy. Smoking was more prevalent in males (31% vs. 15%; P = .009). Free thyroxine and triiodothyronine levels were comparable. ATDs were first-line treatment in all males and in 168 of 171 females, for a median duration of 24 and 20 months, respectively ( P = .55). Remission rates were 47% in men and 58% in women ( P = .14). Males had fewer adverse events (9% vs. 18%) and treatment discontinuation (5% vs. 16%). Disease recurrence was comparable (14% vs. 20%; P = .32), as was requirement for second-line treatment, either radioiodine therapy or thyroidectomy. CONCLUSION: Graves disease presentation is similar in men and women. Men treated with ATDs have high remission rates and similar recurrence rates compared to women, with fewer adverse events and less discontinuation of treatment. ATDs are an attractive first-line treatment for both genders. ABBREVIATIONS: ATA = American Thyroid Association; ATD = antithyroid drug; GO = Graves ophthalmopathy; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone.