The Association Between Thyroid Stimulating Hormone and Depression: A Historical Cohort Study.

OBJECTIVE: To investigate the association between thyroid-stimulating hormone (TSH) and clinically relevant depression (CRD) in a population-based study. PATIENTS AND METHODS: Adult patients (≥18 years of age) who received care at Mayo Clinic in Rochester, Minnesota, and completed a TSH and Patient Health Questionnaire - 9 (PHQ-9) within 6 months of each other, between July 8, 2017, and August 31, 2021, were included. Demographics, medical comorbidities, thyroid function laboratory data, psychotropic medications, presence of primary thyroid disorder, thyroid hormone replacement (T4 and/or T3), and mood disorder diagnoses (using International Classification of Diseases, 10th version, Clinical Modifications codes) were extracted electronically. The primary outcome, CRD, was defined as a PHQ-9 score greater than or equal to 10. Logistic regression analysis was conducted to assess the association between TSH categories (low ≤0.3 mIU/L; normal >0.3-4.2 mIU/L; high >4.2 mIU/L) and CRD. RESULTS: The cohort included 29,034 patients, mean age 51.4 years, 65% females, 89.9% White, and a mean body mass index of 29.9 kg/m2. The mean ± standard deviation for TSH was 3.0±8.5 mIU/L, and the mean PHQ-9 score was 6.3±6.2. After adjustment, the odds of CRD were significantly higher among the low TSH category (odds ratio, 1.37; 95% CI, 1.18-1.57; P<.001) compared with the normal TSH category, especially in people 70 years of age or younger compared with people older than 70 years of age. Subgroup analysis did not show an increase in odds of CRD among patients with subclinical/overt hypothyroidism/hyperthyroidism (after adjustment). CONCLUSION: In this large population-based cross-sectional study, we report that low TSH was associated with higher odds of depression. Future longitudinal cohort studies are needed to investigate the relationship between thyroid dysfunction and depression as well as sex differences.

Thyroid Hormone Augmentation for Bipolar Disorder: A Systematic Review.

Thyroid hormone (TH) augmentation, although commonly used for major depression, is sparingly used for bipolar disorder (BD) after the failure of mood-stabilizing agents. While the exact mechanisms of thyroid hormone action in BD remains unclear, central thyroid hormone deficit has been postulated as a mechanism for rapid cycling. This systematic review-conducted in accordance with the PRISMA guidelines-of eight studies synthesizes the evidence for TH augmentation in BD. A systematic search of the Ovid MEDLINE, Embase, PsycINFO, and Cochrane databases was conducted for randomized controlled trials (RCT), open-label trials, and observational studies of levothyroxine (LT4) and triiodothyronine (T3) for BD. Open-label studies of high dose LT4 augmentation for bipolar depression and rapid cycling showed improvement in depression outcomes and reduction in recurrence, respectively. However, an RCT of high-dose LT4 did not show benefit in contrast to placebo. An RCT comparing LT4, T3, and placebo showed benefit only in rapid-cycling bipolar women. A meta-analysis could not be completed due to significant differences in study designs, interventions, and outcomes. Our systematic review shows mixed evidence and a lack of high-quality studies. The initial promise of supratherapeutic LT4 augmentation from open-label trials has not been consistently replicated in RCTs. Limited data are available for T3. The studies did not report significant thyrotoxicosis, and TH augmentation were well tolerated. Therefore, TH augmentation, especially with supratherapeutic doses, should be reserved for highly treatment-resistant bipolar depression and rapid-cycling BD.

Pure Androgen-Secreting Radiologically Suspicious Adrenal Mass: Benign or Malignant?

Pure androgen-secreting adrenocortical tumors (PASATs) are rare entities. Their clinical presentations include virilizing features that vary based on age and gender. The pathogenesis of this tumor is still unclear, with around 50% of such tumors being malignant. Imaging characteristics of the tumor on CT/MRI including size, heterogenicity, and contrast wash-out time are used to predict malignancy. Surgical excision is recommended for all functional adrenal tumors. In this report, we discuss a case of a 68-year-old postmenopausal female presenting with hyperandrogenism and was found to have a 7-cm, PASAT that raised suspicion for malignancy on CT scan, but was determined to be benign on surgical pathology.

Mobile Virtual Reality Versus Mobile 360° Video to Promote Enrollment in the Diabetes Prevention Program Among Hispanic Adults: Pilot Study.

BACKGROUND: Hispanic adults are at increased risk of developing type 2 diabetes. The Diabetes Prevention Program (DPP) reduces the risk of developing type 2 diabetes; however, the rate of enrollment is very low. OBJECTIVE: The goal of this pilot project was to determine whether presenting brief motivational mobile videos in virtual reality vs 360° video has differential effects on risk perceptions and enrollment in the DPP. METHODS: Adults with prediabetes were recruited at a clinic serving a low-income Hispanic community. After consenting, the participants completed a baseline survey that collected information about demographics and risk perceptions. All participants then viewed 2 videos. Per random assignment, the videos were presented either using the participant's smartphone alone (360° video) or were viewed with their smartphone in a virtual reality (VR) cardboard headset. Two weeks later, a follow-up survey collected measures of enrollment in the DPP, risk perceptions, health literacy, the importance of contextual factors related to the decision of whether to enroll in the DPP (eg, distance to the class), and qualitative feedback on the interventions. We used logistic regression to determine whether enrollment in the DPP differed by intervention mode, while accounting for health literacy and contextual factors related to the DPP. We used unpaired t tests to examine differences in change in risk perceptions between groups. Paired t tests were used to examine within-subject changes in risk perceptions. RESULTS: A total of 116 participants provided complete data. Most participants were middle-aged (mean age 44.6 years; SD 11.9) Hispanic (114/116), female (79/116), with low health literacy (mean score 12.3/20; SD 3.4). Enrollment in the DPP was 44/116 (37.9%) overall but did not differ by group (odds ratio for enrolling in VR group 1.78, 95% CI 0.75-4.3; P=.19). Individuals who rated the distance needed to travel to attend the DPP as more important were less likely to enroll in the DPP (odds ratio 0.56, 95% CI 0.33-0.92; P=.03). Risk perceptions did not differ by group (mean change in 360° video group -0.07, mean change in VR group 0.03, t=0.6, P=.54) and did not change within subjects (mean 0.02, t=0.21, P=.83). Participant feedback suggested that the videos are emotionally engaging and educational. CONCLUSIONS: The videos presented in 360° video and mobile VR had equal efficacy in promoting enrollment in the DPP. Future work to rigorously evaluate this intervention, its mechanism of action, and potential moderators of the efficacy are discussed.

Lithium-Induced Hyperparathyroidism: An Ill-defined Territory.

Lithium is the gold standard treatment for bipolar disorder. Studies have shown an association between lithium and hyperparathyroidism. However, there is limited data regarding the management of lithium-induced hyperparathyroidism. We present a clinical conundrum which physicians frequently encounter-an excellent lithium responder refractory to other treatments who developed lithium-induced hyperparathyroidism. Medical treatment with cinacalcet was successful in management of hyperparathyroidism without discontinuing lithium maintenance therapy.

Bexarotene: A Rare Cause of Misleading Thyroid Function Tests.

Bexarotene is a very rare cause of central hypothyroidism (CH) and its effects have been reported to be dose-dependent; however, the available data in the literature on dose-dependent effects are variable. The standard practice of monitoring thyroid function using thyroid-stimulating hormone (TSH) to adjust levothyroxine (LT4) dose does not apply to bexarotene since it causes CH. In CH, TSH is not reliable. Hence free tetraiodothyronine (fT4) level is used to monitor and adjust the LT4 dose. We report a case of an 81-year-old Caucasian male with cutaneous T-cell lymphoma (CTCL) who was treated with bexarotene. His pre-treatment TSH was normal at 1.6 µIU/mL (reference range: 0.46-4.68 µIU/mL). Post-bexarotene, the total tetraiodothyronine (T4) level was within the reference range, but a downward trend was noted. Eventually, total triiodothyronine (T3) dropped to a low level of 0.61 ng/mL (reference range: 0.97-1.69 ng/mL), and LT4 was initiated. Bexarotene dose was increased, but LT4 was not increased by the primary physician who relied on TSH level, which was low, and hence the existing LT4 dose was maintained. The patient had persistent symptoms of hypothyroidism and, eventually, a diagnosis of CH was made. The symptoms of hypothyroidism improved after normalizing fT4, with an increase in the LT4 dose. This case represents an example of missed CH due to bexarotene, -which led to suboptimal LT4 replacement impacting the quality of life for the patient.

Medications Affecting the Biochemical Conversion to Type 2 Diabetes: A Systematic Review and Meta-Analysis.

CONTEXT: The extent to which some pharmacological interventions reduce or increase the risk of biochemical conversion to type 2 diabetes mellitus (T2DM) in at-risk individuals is unclear. METHODS: We searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, and Scopus through 24 August 2017 for randomized controlled trials evaluating the effect of drugs suspected to modify the risk of biochemical conversion to T2DM. RESULTS: We included 43 trials with 192,156 subjects (mean age, 60 years; 56% men; mean body mass index, 30.4 kg/m2). α-Glucosidase inhibitors, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, metformin, orlistat, phentermine/topiramate, and pioglitazone significantly reduced the risk of biochemical conversion to T2DM, whereas statins and nateglinide increased the risk. There was insufficient direct evidence regarding the effects of sulfonylureas, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors. Most trials were brief and evaluated this outcome during treatment without a withdrawal or washout period. CONCLUSIONS: Several drugs modify the risk of biochemical conversation to T2DM, although whether this effect is persistent and clinically relevant is unclear. Future studies need to focus on cardiovascular disease prevention, mortality, and patient-important outcomes instead of biochemical conversion to T2DM.

Comparative Effectiveness of Treatment Choices for Graves' Hyperthyroidism: A Historical Cohort Study.

BACKGROUND: The optimum therapy for Graves' disease (GD) is chosen following discussion between physician and patient regarding benefits, drawbacks, potential side effects, and logistics of the various treatment options, and it takes into account patient values and preferences. This cohort study aimed to provide useful information for this discussion regarding the usage, efficacy, and adverse-effect profile of radioactive iodine (RAI), antithyroid drugs (ATDs), and thyroidectomy in a tertiary healthcare facility. METHODS: The cohort included consecutive adults diagnosed with GD from January 2002 to December 2008, who had complete follow-up after treatment at the Mayo Clinic, Rochester, Minnesota. Data on treatment modalities, disease relapses, and adverse effects were extracted manually and electronically from the electronic medical records. Kaplan-Meier analyses were performed to evaluate the association of treatments with relapse-free survival. RESULTS: The cohort included 720 patients with a mean age of 49.3 years followed for a mean of 3.3 years. Of these, 76.7% were women and 17.1% were smokers. The initial therapy was RAI in 75.4%, ATDs in 16.4%, and thyroidectomy in 2.6%, while 5.6% opted for observation. For the duration of follow-up, ATDs had an overall failure rate of 48.3% compared with 8% for RAI (hazard ratio = 7.6; p < 0.0001). Surgery had a 100% success rate; 80% of observed patients ultimately required therapy. Adverse effects developed in 43 (17.3%) patients treated with ATDs, most commonly dysgeusia (4.4%), rash (2.8%), nausea/gastric distress (2.4%), pruritus (1.6%), and urticaria (1.2%). Eight patients treated with RAI experienced radiation thyroiditis (1.2%). Thyroidectomy resulted in one (2.9%) hematoma and one (2.85%) superior laryngeal nerve damage, with no permanent hypocalcemia. CONCLUSIONS: RAI was the most commonly used modality within the cohort and demonstrated the best efficacy and safety profile. Surgery was also very effective and relatively safe in the hands of experienced surgeons. While ATDs allow preservation of thyroid function, a high relapse rate combined with a significant adverse-effect profile was documented. These data can inform discussion between physician and patient regarding choice of therapy for GD.

Primary Hypothyroidism with Exceptionally High Prolactin-A Really Big Deal.

BACKGROUND: Primary hypothyroidism can cause both hyperprolactinemia and pituitary hyperplasia. The degree of hyperprolactinemia is generally modest, and rarely do prolactin concentrations exceed 100 ng/mL (4.34 nmol/L). This combination of hyperprolactinemia and pituitary gland enlargement might raise suspicion for a prolactinoma or a nonfunctioning adenoma limiting the ability of hypothalamic dopamine to inhibit prolactin production, the so-called "stalk effect." CASE DESCRIPTION: We describe a 30-year-old female with headaches, galactorrhea, and hyperprolactinemia with a presumptive diagnosis of a prolactinoma. She had hypothyroidism after treatment of Graves disease at age 17 years but was noncompliant with levothyroxine replacement. Thyroid-stimulating hormone (TSH) was 263 mIU/L, FT4 was 3.01 pmol/L, and prolactin was 323 ng/mL (14.06 nmol/L). Magnetic resonance imaging (MRI) demonstrated increased volume of the pituitary gland with homogeneous enhancement with gadolinium. Levothyroxine treatment for 2 weeks decreased her TSH to130 mIU/L, but her total prolactin remained elevated at 386 ng/mL (16.78 nmol/L). Further testing identified that 76% of the total prolactin was macroprolactin. CONCLUSIONS: Primary hypothyroidism can cause hyperprolactinemia, and prolonged disease may lead to pituitary hyperplasia. However, a marked elevation of prolactin should raise suspicion to investigate additional etiologies for hyperprolactinemia. Our case exemplifies a dual etiology for hyperprolactinemia and pituitary hyperplasia caused by both hypothyroidism and macroprolactin. This knowledge is invaluable for clinicians to avoid unnecessary management with dopamine agonists and/or surgery. This patient's prolactin was 323 ng/mL (14.06 nmol/L). Before our case, the highest prolactin in a hypothyroid patient reported in the literature was 253 ng/mL (11.0 nmol/L).

From hypocalcemia to hypercalcemia-an unusual clinical presentation of a patient with permanent postsurgical hypoparathyroidism.

CONTEXT: Hypercalcemia associated with lymphomas can be secondary to increased calcitriol [1,25(OH)2 vitamin D3], PTHrP, or osteolytic metastases. OBJECTIVE: A case of calcitriol-mediated hypercalcemia secondary to non-Hodgkin lymphoma in a patient with postsurgical hypoparathyroidism is presented. DESIGN AND SETTING: Single patient managed at a tertiary health care facility in the United States. PATIENT: A 55-year-old white woman had a total thyroidectomy and radioiodine ablation for a 3.5-cm follicular carcinoma. Surgery was complicated by permanent hypoparathyroidism treated with calcium, calcitriol, and cholecalciferol. For over 16 years she had no evidence of either residual thyroid tissue in the neck or metastasis. Her corrected serum calcium levels were appropriately maintained in the low-normal range. During a routine clinic visit, she had mild hypercalcemia; calcium and cholecalciferol were reduced by 50%, while calcitriol was continued. Two weeks later, she presented with nausea, abdominal pain, and multiple rapidly enlarging cervical and axillary lymph nodes with elevated calcium and calcitriol. A fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography scan and lymph node biopsy were diagnostic for non-Hodgkin lymphoma. INTERVENTION: Calcium and calcitriol were stopped; hypercalcemia was corrected with iv fluids. Chemotherapy resulted in an excellent response within 7 weeks; calcitriol normalized, and the patient developed recurrent hypocalcemia. Positron emission tomography/computed tomography scans at 7 weeks and 3 months after treatment documented near-complete resolution of the lesions. Outcome and Result: Sixteen months after the treatment of lymphoma, the patient remains free of disease and is on calcium, calcitriol, and cholecalciferol. CONCLUSION: Clinicians should have a high index of suspicion for malignancy when patients presents with rapid and high elevations of serum calcium.

Screening for gestational diabetes: a systematic review and meta-analysis.

CONTEXT: Gestational diabetes mellitus (GDM) is defined as any degree of hyperglycemia with first recognition during pregnancy. The optimal time to screen for GDM that would maximize the yield and benefits remains unclear. OBJECTIVE: Our objective was to appraise the evidence regarding screening for GDM (accuracy, correlation with adverse outcomes, and harms). DATA SOURCES: We searched Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011. STUDY SELECTION: We included randomized controlled trials and observational studies that enrolled pregnant woman who were evaluated using different GDM screening tests. DATA EXTRACTION: Two reviewers working independently abstracted the data. RESULTS: We did not find any randomized controlled trials of GDM screening that measured feto-maternal outcomes. A 1-hour 50-g glucose challenge test with a cutoff point at 140 mg/dL was the most commonly used screening method. The results of this test were statistically associated with feto-maternal outcomes (P < .001), even though only 11% of individuals with a positive test (according to Carpenter and Coustan criteria) developed GDM. Positive Carpenter and Coustan criteria were associated with macrosomia (odds ratio [OR] = 2.4, 95% confidence interval [CI] = 1.9-3.1, P < .001) and gestational hypertension (OR = 1.7, CI = 1.3-2.1, P < .001). Positive National Diabetes Data Group criteria were also associated with macrosomia (OR = 3.2, CI = 2.3-4.4, P < .001) and gestational hypertension (OR = 2.1, CI = 1.6-2.8, P < .001). CONCLUSIONS: Indirect evidence supports the use of contemporary screening tests for GDM to identify pregnancies at increased risk of adverse feto-maternal outcomes. It also suggests that use of these tests will place some women under unnecessary treatment for GDM.

Glucose targets in pregnant women with diabetes: a systematic review and meta-analysis.

BACKGROUND: Glucose-lowering treatments are used during pregnancy to reduce the risk for complications in the mother and offspring, yet treatment targets have not been established. OBJECTIVE: Our objective was to appraise and summarize the available evidence regarding the association between different blood glucose targets during pregnancy and fetal and maternal outcomes. METHODS: We searched Medline, EMBASE, Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL through May 2011 for randomized trials and observational studies that enrolled women with diabetes during pregnancy and reported planned or achieved glucose targets. We used random-effects meta-regression models to estimate the odds ratio for the association of outcomes of interest and glucose targets. When possible, we adjusted for diabetes type, trimester, and diabetes treatment. RESULTS: We included 34 studies enrolling 9433 women. The studies had moderate to high risk of bias due to evidence of reporting bias and insufficient adjustment for important covariates, particularly maternal body mass index. A fasting glucose target of <90 mg/dL was the most commonly reported and the one most strongly associated with reduced risk of macrosomia (odds ratio = 0.53, 95% confidence interval = 0.31-0.90, P = .02) for women with gestational diabetes during the third trimester. For type 1 and type 2 diabetes, and for pre- and postprandial targets, data were sparse and inconclusive. CONCLUSIONS: Evidence warranting very low confidence in the estimates suggests that a fasting glucose target of <90 mg/dL is associated with a lower risk of macrosomia and other outcomes of different importance in women with gestational diabetes. Whether this target can be extrapolated to women with pregestational diabetes or whether targets above or below this threshold offer a better benefit/risk balance remains unclear.

Adverse effects of the common treatments for polycystic ovary syndrome: a systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is common among women of childbearing age and the available pharmacological therapies have different side-effect profiles. OBJECTIVE: We summarized the evidence about the side effects of oral contraceptive pills, metformin, and anti-androgens in women with PCOS. DATA SOURCE: Sources included Ovid Medline, OVID EMBASE, OVID Cochrane Library, Web of Science, Scopus, PsycInfo, and CINAHL from inception through April 2011. STUDY SELECTION: We included comparative observational studies enrolling women with PCOS who received the agents of choice for at least 6 months and reported adverse effects. DATA EXTRACTION: Using a standardized, piloted, and Web-based data extraction form and working in duplicate, we abstracted data from each study and performed meta-analysis when possible. DATA SYNTHESIS: We found 22 eligible studies of which 20 were randomized. No study reported severe side effects (eg, lactic acidosis, thromboembolic episodes, liver toxicity, cancer incidence, or pregnancy loss). Meta-analysis demonstrated no significant change in weight in oral contraceptive pills or flutamide users. Indirect evidence from populations without PCOS demonstrated no increased risk of lactic acidosis with metformin, only case reports of liver toxicity with flutamide (no comparative evidence), and increased relative risk difference of venous thromboembolism with oral contraceptive pills but very low absolute risk. Evidence on mortality, cardiovascular mortality, and cancer was inconclusive. CONCLUSIONS: Drugs commonly used to treat PCOS appear to be associated with very low risk of severe adverse effects although data are extrapolated from other populations.

Lifestyle modification programs in polycystic ovary syndrome: systematic review and meta-analysis.

CONTEXT: Polycystic ovary syndrome (PCOS) is a prevalent disorder that affects women of childbearing age and may be related to obesity and insulin resistance. OBJECTIVE: The purpose of this systematic review was to appraise the evidence of the impact of lifestyle modification (LSM) interventions on outcomes of women with PCOS. DATA SOURCES: Sources included Ovid Medline, OVID Embase, OVID Cochrane Library, Web of Science, Scopus, PsycINFO, and CINAHL (up to January 2011). STUDY SELECTION: We included randomized controlled trials that enrolled woman of any age with PCOS who received LSM and compared them against women who received no intervention, minimal intervention, or metformin. DATA EXTRACTION: Two authors performed the data extraction independently. DATA SYNTHESIS: We included 9 trials enrolling 583 women with a high loss to follow-up rate, lack of blinding, and short follow-up. Compared with minimal intervention, LSM significantly reduced fasting blood glucose (weighted mean difference, -2.3 mg/dL; 95% confidence interval, -4.5 to -0.1, I² = 72%, P = .04) and fasting blood insulin (weighted mean difference, -2.1 µU/mL, 95% confidence interval, -3.3 to -1.0, I² = 0%, P < .001). Changes in body mass index were associated with changes in fasting blood glucose (P < .001). Metformin was not significantly better than LSM in improving blood glucose or insulin levels. We found no significant effect of LSM on pregnancy rate, and the effect on hirsutism was unclear. CONCLUSIONS: The available evidence suggests that LSM reduces fasting blood glucose and insulin levels in women with PCOS. Metformin has similar effects. Translation of these short-term effects to patient-important outcomes, beyond diabetes prevention, remains uncertain.

Comparative effectiveness of therapies for Graves' hyperthyroidism: a systematic review and network meta-analysis.

CONTEXT: Several treatment options are available for Graves' disease (GD), including antithyroid drugs (ATDs), radioactive iodine (RAI), and thyroidectomy. OBJECTIVE: The primary outcome was to determine the relapse rates of various treatment options. The secondary outcome was to present data regarding adverse effects of ATDs. DATA SOURCES: We searched multiple databases through March 2012. STUDY SELECTION: Eligible studies were randomized clinical trials and comparative cohort studies in adults that included 2 or more treatment options for GD. DATA EXTRACTION: Two reviewers independently selected studies, appraised study quality, extracted outcome data, and determined adverse effect profiles. DATA SYNTHESIS: We found 8 studies with 1402 patients from 5 continents. Mean follow-up duration in months was: ATDs, 57; RAI, 64; and surgery, 59. Studies were at moderate to high risk of bias. Network meta-analysis suggested higher relapse rates with ATDs (52.7%; 352 of 667) than RAI (15%, 46 of 304) (odds ratio = 6.25; 95% confidence interval, 2.40-16.67) and with ATDs than surgery (10%; 39 of 387) (odds ratio = 9.09; 95% confidence interval, 4.65-19.23). There was no significant difference in relapse between RAI and surgery. Examination of 31 cohort studies identified adverse effects of ATDs in 692 of 5136 (13%) patients. These were more common with methimazole, mainly owing to dermatological complications, whereas hepatic effects were more common with propylthiouracil use. CONCLUSION: We confirm the relatively high relapse rate of ATD therapy in comparison with RAI or surgery, along with a significant side effect profile for these drugs. These data can inform discussion between physicians and patients regarding the choice of therapy for GD. The limited quality of the evidence in the literature underlines the need for future randomized clinical trials in this area.