Normal Thyroid Hormone Research Articles

The dangerous trend of levothyroxine medicalization

Thyroid hormone replacement is paramount in overt hypothyroidism; recently, however, thyroid hormone substitution is increasingly prescribed to patients with normal thyroid hormone levels. This forum article discusses the complex causes and the possible negative effects of overusing thyroid hormone replacement drugs.

Pharmacodynamic and pharmacokinetic properties of the combined preparation of levothyroxine plus sustained- release liothyronine; a randomized controlled clinical trial

BackgroundUnderstanding pharmacokinetics (PK) and pharmacodynamics (PD) of the sustained-release liothyronine (SR-T3) is of paramount importance to design therapeutic regimens that are able to simulate normal thyroid hormone secretion while avoiding excursions in the T3 serum concentration. Here, we designed a parallel randomized clinical trial to characterize the PK and PD of the combined preparations of LT4 + SR-T3 in hypothyroid patients.MethodsRadioiodine-treated hypothyroid patients over 20 years of age, who attained euthyroidism with LT4 monotherapy were recruited from the Endocrine Clinic in Tehran. The patients were allocated to two intervention groups of group A: 9 µg SR-T3 plus 68.5 μg LT4 (ratio 1:7.5) and group B: 12 µg SR-T3 plus 60 µg LT4 (ratio 1:5), and a control group with LT4 monotherapy. For PD study, thyroid hormone profile was evaluated at 8 and 12 weeks intervals after intervention. To assess PK properties of SR-T3, T3-Cmax, T3-Tmax and AUC0 − 24 were calculated at the last visit.ResultsSerum T4 and FT4 concentrations decreased in the intervention groups after 3 months. No significant difference was observed in serum T3 and FT3 concentrations before and after intervention. Serum T3/T4 ratio increased significantly in the intervention groups after intervention, with the highest increase in group B from 8.6 ± 2.03 at baseline to 12.2 ± 1.6. Comparison of trial groups at follow-up showed no differences in serum TSH, T4, T3 and T3/T4 concentrations among different groups. During 24 h, minimal variation in serum T3 concentration was observed in group B with mean ∆T3 of 15.4 ± 10.5 ng/dl. T3-Tmax, T3-Cmax and AUC0 − 24 in the combined sustained-release preparation were 4.38 ± 1.1 h., 101.0 ± 5.7 ng/dl and 2257 ± 110 ng.h/L, respectively which were significantly different from the control group.ConclusionCombined treatment with a single dose of SR-T3 plus LT4 is associated with increased serum T3/T4 ratio and minimal excursions in serum T3 concentration during 24 h; however, it was not significantly different from the control group. To incorporate sustained-release T3 in the management of hypothyroidism, a higher ratio of SR-T3 to LT4 than that of the previously recommended by the international organizations is suggested.IRCT registration numberIRCT20100922004794N13. https://www.irct.ir/search/result?query=IRCT20100922004794N13. Registration date: 08/12/2021.

The conundrum of acute onset midline neck swellings: a unique case report of a thyroid abscess

The conditions of the thyroid gland are the most common causes for midline neck swellings and present with a spectrum of clinical features and differential diagnosis, some more fatal than the others. One such rare yet worrisome condition is suppurative thyroiditis progressing to an abscess. A 17 year old male presented with an acute neck swelling with fever, pain, and hoarseness of voice. Investigations revealed leucocytosis with normal thyroid hormone levels. Contrast enhanced CT scan of the neck showed presence of an abscess of the thyroid gland with left sided tracheal shift. Incision and drainage with antibiotic support was done leading to an uneventful recovery. The thyroid gland by virtue of its capsule, rich blood supply, and high iodine content is resistant to infection. Thyroid abscess is a rare condition with high morbidity and mortality. This condition should be a differential diagnosis in cases of acute onset midline swellings. Immediate surgical drainage of the collection with antibiotic support is the gold standard treatment of this condition.

Changes in brain structure in subjects with resistance to thyroid hormone due to THRB mutations

BackgroundBeing critical for brain development and neurocognitive function thyroid hormones may have an effect on behaviour and brain structure. Our exploratory study aimed to delineate the influence of mutations in the thyroid hormone receptor (TR) ß gene on brain structure.MethodsHigh-resolution 3D T1-weighted images were acquired in 21 patients with a resistance to thyroid hormone ß (RTHß) in comparison to 21 healthy matched-controls. Changes in grey and white matter, as well as cortical thickness were evaluated using voxel-based morphometry (VBM) and diffusion tensor imaging (DTI).ResultsRTHß patients showed elevated circulating fT4 & fT3 with normal TSH concentrations, whereas controls showed normal thyroid hormone levels. RTHß patients revealed significantly higher scores in a self-rating questionnaire for attention deficit hyperactivity disorder (ADHD). Imaging revealed alterations of the corticospinal tract, increased cortical thickness in bilateral superior parietal cortex and decreased grey matter volume in bilateral inferior temporal cortex and thalamus.ConclusionRTHb patients exhibited structural changes in multiple brain areas. Whether these structural changes are causally linked to the abnormal behavioral profile of RTHß which is similar to ADHD, remains to be determined.

Lower free triiodothyronine levels are associated with higher all-cause and cardiovascular mortality in people with diabetes-NHANES 2007–2012

ObjectiveThyroid hormone plays a key role in maintaining cardiovascular system homeostasis. However, there is limited evidence regarding the correlation between normal range thyroid hormone levels and all-cause mortality or cardiovascular mortality among individuals with diabetes. MethodThis retrospective study analyzed data from 1,208 individuals with diabetes who participated in the National Health and Nutrition Survey (NHANES) conducted in the United States between 2007 and 2012. Weighted Kaplan-Meier (KM) analysis and Cox proportional hazards models were used to explore the association between thyroid hormone indices and mortality. ResultsThe Weighted Kaplan-Meier (KM) analysis revealed statistically significant differences in survival probabilities across free triiodothyronine (FT3), free thyroxine (FT4), FT3/FT4 ratio and thyroid-stimulating hormone (TSH) groups (p < 0.05 or < 0.001). In the multivariate adjusted Cox proportional hazards models, higher levels of FT3 were founded to be associated with decreased all-cause mortality (HR (95% CI), 0.715 (0.567, 0.900)), cardio-cerebrovascular mortality (0.576 (0.408, 0.814)) and cardiovascular mortality (0.629 (0.438, 0.904)). Notably, this correlation was more significant among individuals over the age of 60, as indicated by the results of the nonlinear regression analysis. ConclusionFT3 is an independent predictor of all-cause death, cardio-cerebrovascular and cardiovascular death in euthyroid subjects with diabetes.

Alterations in serum Thyroid and Reproductive hormone levels in occupationally exposed pesticides sprayers

Background: Pesticides contain endocrine disrupting chemicals that have potential to perturb the normal thyroid and reproductive hormone axis. The aim of present study was to estimate the variations in serum tri-iodothyronine (T3) tetra-iodothyronine (T4) thyroid stimulating hormone (TSH) and testosterone levels in occupationally exposed pesticide sprayers in comparison to controls.&#x0D; Methods: For this purpose, blood samples of (n=50) pesticide sprayers were collected from District Layyah, south Punjab, Pakistan. Whereas, samples (n=25) of healthy control subjects were obtained from University of the Punjab, Lahore. Levels of T3, T4, TSH and testosterone in the serum were estimated by ELISA technique. The data obtained was analyzed by applying Un-paired Student “t” test at with significance level of P &lt; 0.05. Graph pad prism version 6.0 software was utilized for statistical interpretation.&#x0D; Results: Pronounced (P &lt; 0.0001) decrease of both T3 and T4, whereas, a significant increase in TSH (P = 0.005) level was evidenced in pesticide sprayers as compared to controls. Moreover, a significant decrease (P &lt; 0.001) was noted in the level of testosterone in pesticide sprayers as compared to controls.&#x0D; Conclusion: Pertinently, the pesticides are a potent source of inducing imbalances in T3, T4, TSH, and testosterone secretion. Pesticide sprayers are, therefore, recommended to use prophylactic measures like wearing face masks and opt safer protocols in order to avoid direct hazardous exposure to endocrine disrupting chemicals.

ASSOCIATION OF THYROID HORMONE LEVELS AND CHRONIC KIDNEY DISEASE

Introduction- Normal thyroid hormone metabolism, breakdown, and excretion depend heavily on the kidney. We sought to assess the serum thyroid hormone levels in CKD patients in the current investigation because there is little data on the association between thyroid hormone levels and CKD. Methods- This cross-sectional and time bound study was conducted in department of General Medicine and Nephrology in NIMS&amp;R Hospital, Jaipur for 18 months. Results- Number of patients with low serum T3 levels increased proportionately with decreasing eGFR levels. Serum T4 and TSH levels were not signicantly related to worsening renal function. Conclusion- Low T3 syndrome was the commonest and subclinical hypothyroidism was the second most common thyroid abnormality detected. Hypothyroidism and severity of CKD did not correlate with each other.

Alterations of Thyroid Hormone Levels and the Risks of Diabetic Retinopathy in T2DM

Background: Diabetes mellitus and thyroid disease are linked endocrinopathies. The association between diabetes mellitus complications and thyroid function is characterized by a complicated interdependent interplay that is difficult to understand. Objective: We conducted this study to determine the association between diabetic retina disease (DRD) incidence and normal thyroid hormone levels in T2DM. Methods: Recruit patients in the study, 134 patients with type 2 diabetes and 36 healthy ones with no DM, were screened in the present case-control study. Diabetic retinopathy was tested for all patients, and anthropometric and thyroid functions were assessed. Regression analyses were employed to evaluate the relationship between thyroid hormones and the risk of developing DR. Results: There were significant differences in triiodothyronine (T3) and thyroxine (T4) serum levels among the DR groups and the healthy control. The levels in each TSH and T4 are positively significant between groups of PDR and NDR, while T3 was negatively associated with NPDR. A significant association was found between increasing levels of T3 and the development of severe DR; thus, PDR was less likely to occur in individuals with high T3 levels‎ [OR 0.014(95% CI, 0.001-0.34) P value is 0.009 after adjustment. The risk of PDR had an increased likelihood of developing PDR at the highest levels of serum TSH and T4 [OR 41.07(1.60-1053.1) P= 0.025, OR 65.91(2.10-2067) P= 0.017, respectively). Conclusion: Diabetes retinopathy in euthyroid Iraqi people may be associated with levels of T3 and T4 in the blood. Patients with higher TSH and T4 concentrations had a greater risk of developing sight-threatening PDR in type 2 diabetics.

A Positive Newborn Screen for Congenital Hypothyroidism in a Clinically Euthyroid Neonate—Avoiding Unnecessary Treatment

Newborn screening for congenital hypothyroidism (CH) has dramatically improved the neurocognitive outcomes for newborns with a confirmed positive screening test result. However, screening yields a small number of false positive and false negative results. This report describes the first known case of familial dysalbuminaemic hyperthyroxinaemia presenting with a positive newborn thyroid stimulating hormone screen. This condition is characterized by artefactually elevated free tetraiodothyronine (T4) and triiodothyronine (T3) levels due to increased albumin binding and subsequent dissociation during laboratory assays but normal true free thyroid hormone and thyroid stimulating hormone (TSH) levels in a clinically euthyroid subject. This highlights the need to take care when attributing clinical significance to discordant results.

Characteristics and clinical course of thyroid abnormalities arisen in long term survivors of childhood cancer

BackgroundThyroid abnormality is a common late effect seen in childhood cancer survivors (CCSs). We analyzed the prevalence and risk factors of thyroid abnormalities based on diagnoses and treatment modalities in CCSs.MethodsThe medical records of 257 CCSs who were diagnosed with cancer less than 20 year of age were retrospectively reviewed. The median age was 11.8 years (0.1–19.8). The median follow-up period after completion of therapy was 9.6 years (5.0–19.5).ResultsOf 257 subjects, thyroid abnormalities were identified in 107 (41.6%). Sixty-five out of 257 (25.3%) had subclinical hypothyroidism, and 16 (6.2%) developed central hypothyroidism. Five CCSs (1.9%) had primary overt hypothyroidism. Five (1.9%) and 6 (2.3%) CCSs were diagnosed with autoimmune thyroiditis and thyroid cancer, respectively. Among the different diagnostic groups, thyroid abnormalities were frequent in the brain tumor or Hodgkin disease or nasopharyngeal cancer groups. CCSs who received irradiation directly or near hypothalamus-pituitary-thyroid (HPT) axis had more thyroid abnormalities compared to the rest CCSs (P < 0.0001). CCSs who were treated with SCT had an increased prevalence of thyroid abnormalities (60.5%) compared to the other CCSs (37.9%) (P = 0.0069). Forty-five (42%) of 107 subjects with thyroid abnormalities had normalized thyroid hormone levels at the last follow-up. Irradiation directly or near HPT axis were thought to be a predicting factor of persistent subclinical hypothyroidism.ConclusionsSubclinical hypothyroidism was common in CCSs. CCSs with irradiation directly or near HPT axis were at risk for persistent thyroid dysfunction.

Association Between Sensitivity to Thyroid Hormone Indices and Diabetic Retinopathy in Euthyroid Patients with Type 2 Diabetes Mellitus.

Normal thyroid hormone (TH) levels and their relation to microvascular complications in patients with type 2 diabetes mellitus (T2DM) have been studied. However, the relationship between TH sensitivity and diabetic retinopathy (DR) remains unclear. Thus, this study aimed to investigate the relationship between TH sensitivity and the risk of DR in euthyroid T2DM patients. This retrospective study analyzed 422 T2DM patients and calculated their sensitivity to TH indices. Multivariable logistic regression, generalized additive model, and subgroup analysis were performed to examine the association between sensitivity to TH indices and DR risk. After adjusting for covariates, the binary logistic regression model showed no statistically significant association between the sensitivity of TH indices and the risk of DR in euthyroid T2DM patients. However, a non-linear relationship was found between sensitivity to TH indices (thyroid-stimulating hormone index, thyroid feedback quantile index [TFQI]) and the risk of DR in the crude model; TFQI and DR in the adjusted model. The inflection point of the TFQI was 0.23. The effect size (odds ratio) on the left and right of the inflection point were 3.19 (95% confidence interval [CI]: 1.24 to 8.17 p=0.02) and 0.11 (95% CI: 0.01, 0.93 p=0.04), respectively. Moreover, this relationship was maintained by men stratified by sex. In euthyroid patients with T2DM, an approximate inverted U-shaped relationship and a threshold effect were demonstrated between TH index sensitivity and DR risk with sex differences. This study provided an in-depth understanding of the relationship between thyroid function and DR, which has important clinical implications for risk stratification and individual prediction.

Relation between thyroid hormonal status, neutrophillymphocyte ratio and left ventricular systolic function in patients with acute coronary syndrome.

Aim To examine a relation of thyroid function, neutrophil-lymphocyte ratio (NLR) with left ventricular function measured through the left ventricular ejection fraction (LVEF) in patients with acute myocardial infarction treated with percutaneous coronary intervention (PCI). Methods This prospective research involved 160 consecutive patients with acute myocardial infarction. Patients were divided into those with normal thyroid hormone status (n=80) and those with hypothyroidism (newly diagnosed) (n=80). Inflammatory parameters and parameters of hormonal status were taken for analysis: thyroid-stimulating hormone (TSH), thyroxine (T4), triiodothyronine (T3), free thyroxine (FT4), and free triiodothyronine (FT3). All patients underwent transthoracic echocardiographic examination (TTE) five days upon admission, and left ventricular ejection fraction (LVEF) was analysed. Results Significant difference between the two groups was verified in values of T3, T4, erythrocytes, haemoglobin, haematocrit, neutrophil, lymphocytes, NLR, C-reactive protein (CRP) and sedimentation rate. Patients with euthyroidism had a higher frequency of coronary single-vessel disease (p=0.035) and a significantly lower frequency of triple vessel disease (p=0.046), as well as a higher median value of LVEF (p=0.003). There was a significant correlation between LVEF with haemoglobin values (p=0.002), NLR (p=0.001), and CRP (p=001). Conclusion The altered status of the thyroid gland in acute myocardial infarction is associated with the severity of the coronary blood vessel lesion, LVEF and correlates with inflammatory response.

Evaluation of an Association of Thyroid Disorder and Dyslipidemia in Patients with Cardiovascular Disease: A Cross-sectional Study

Background: Subclinical Hypothyroidism (SCH) is defined as normal serum free thyroid hormone levels coexisting with elevated serum Thyroid-Stimulating Hormone (TSH) levels. SCH is a common condition observed in clinical practice with several unique features. The present study was conducted to find prevalence of subclinical hypothyroidism in patients with myocardial infarction and demographic differences between patients with and without SCH. Materials and Methods: A total of 100 patients with Myocardial Infarction of Adult (age &gt; 18 years) males and females were selected from the patients attending Medicine OPD, IPD or Intensive Care Unit (ICU) in GMC, Azamgarh. Clinical examination, laboratory investigations for myocardial infarction, thyroid status and lipid profile was done in all patients in our study. All Patients with TSH values &gt; 10mU/L or &lt; 0.04mU/L or Known cases of Thyroid abnormalities were excluded from the study. Statistical analysis was done using excel and SPSS software. Results: Out of 100 patients 44 patients of MI had subclinical hypothyroid were as rest 56 patients were euthyroid. In both the groups no statistical difference was seen in the type of Myocardial infarction. There was significant difference in lipid profile (p&lt;0.05) in SCH group as compared to euthyroid group. Conclusion: Patients with Subclinical hypothyroid and MI had more lipid abnormalities as compared to Euthyroid group although the type of myocardial infarction was similar in both the groups. Males had more myocardial infarction as compared to females in both the subclinical hypothyroid and euthyroid groups.

Challenges in Thyroid Function Testing: Interferences and Clinical Implications

In recent decades, significant advancements have been made in the methodologies used for evaluating thyroid dysfunctions. These advancements include the development of radioimmunoassays, immunometric assays, and liquid chromatography coupled with mass spectrometry. The main thyroid function tests include thyroid-stimulating hormone (TSH) and the measurement of triiodothyronine (T3) and thyroxine (T4), including their total and free fractions. Over time, different generations of TSH tests have been developed, starting from radioimmunoassays to immunometric assays, and more recently, tests utilizing fluorophores and chemiluminescent molecules. The third-generation tests are currently the most widely used due to their high sensitivity and specificity. Thyroid-stimulating hormone is preferred as the initial test for evaluating thyroid function since it has a log-linear relationship with free T4 levels, enabling the identification of subclinical hypothyroidism and subclinical hyperthyroidism. The reference range for normal TSH levels is typically between 0.45 and 4.5 mIU/L. However, there can be variations in TSH levels based on factors such as sex, age, and ethnicity. Specific reference values may be required for certain populations, such as the elderly, pregnancy, and neonates. In the elderly, an increase in TSH levels is expected. In the neonatal period, TSH levels are high after birth and take a few weeks to normalize. During pregnancy, various physiological changes occur, leading to alterations in thyroid hormones to meet fetal demands. Laboratory interferences in thyroid hormone assays must be considered to ensure accurate results. Biotin interference can lead to falsely low TSH and falsely high free T3 and T4 levels. Macro-thyrotropin can cause elevated TSH levels with normal thyroid hormone levels. Heterophilic antibodies can also cause false results. Additionally, the evaluation of autoantibodies and markers used in thyroid cancer follow-up needs special attention. Patients experiencing conditions like trauma, particularly in severe cases, may undergo changes in thyroid hormone levels, even without having a specific thyroid disease, which is called low triiodothyronine syndrome. In conclusion, it is essential to be aware of potential laboratory interferences and consider individual variations to ensure accurate interpretation and appropriate management of patients.

Study of thyroid function among COVID-19-affected and non-affected people during pre and post-vaccination.

The novel coronavirus COVID-19 has caused a global pandemic with many long-ranging effects on the physiological balance of the human body. The impact of COVID-19 on the thyroid axis remains uncertain. Our aim was to assess the long-term consequences of COVID-19 infection and its vaccination with thyroid hormones. Thirty laboratory-confirmed COVID-19-positive patients with no vaccination record, thirty COVID-19-negative patients with vaccination records, and ten healthy subjects were retrospectively, and cross-sectionally enrolled in this study. An ELISA assay was performed to evaluate thyroid function tests, including the total triiodothyronine (TT3), total thyroxine (TT4), and thyroid stimulating hormone (TSH). We found decreased levels of TT3, average or low plasma T4 levels, and standard or slightly decreased TSH levels in unvaccinated COVID-19-positive patients than in the healthy group, while the vaccinated COVID-19-negative group had normal thyroid hormone levels compared to controls. The correlation between TT3 and TSH levels gradually shifted from no association to a negative pattern in the unvaccinated COVID-19-positive group. Again, a highly significant negative correlation between TSH and TT3 was observed on days above 150, although a slight fluctuation was noted on day 90. This pilot study from Bangladesh shows that abnormalities in thyroid function can be observed during COVID-19 infection and after vaccination, which gradually recovers over time.

Isolated growth hormone deficiency and amenorrhea – Case report

Growth hormone (GH) deficiency is the most common hypopituitarism disorder. We highlight the challenges to its diagnosis and management in the setting of a developing country. A 14-year-old came with a chief complaint of inability to menstruate. Menarche was at 12-years old, lasted 7 days, soaking 2 pads/day which discontinued shortly after. Thelarche was at 12-years-old and her breast is at Tanner stage 3. Her axillary and pubic hair are at Tanner stage 1. Height was 120 cm, weight 34.8 kg, height for age z-score<-3. Her lab results were normal for estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin. Bone age was suitable for age. Magnetic resonance imaging revealed pituitary gland hypoplasia (5.3 mm). A hormonal panel 3 years prior showed abnormally low GH level but normal cortisol and thyroid hormone levels. She was diagnosed with isolated growth hormone deficiency (IGHD) with delayed puberty. She was treated with medroxyprogesterone tablets once daily, after which her menstruation restarted. However, due to her economic background, she declined genetic tests, discontinued her medication and amenorrhea recurred. Amenorrhea present after a brief menarche should alert gynaecologists of a possible multi-hormone disorder with an underlying structural abnormality. IGHD may be due to a structural abnormality, such as pituitary gland hypoplasia. Unfortunately, economic reasons prevented the patient from receiving optimal treatment. IGHD rarely presents with a gynaecological complaint. Hormonal and genetic tests along with imaging should be undertaken. Growth hormone supplementation is the treatment of choice.

Reduction in experimental autoimmune thyroiditis by IgG Fc fragments bearing regRF epitopes.

Previously, we identified a new immunoregulatory factor, the production of which provides rats with resistance to certain experimental autoimmune diseases. It has been named regulatory rheumatoid factor (regRF). RegRF inhibits the expansion of CD4 T lymphocytes by killing activated cells. CD4 T cells are essential for antibody production against a majority of antigens and for the generation of cytotoxic T cells; therefore, regRF is an attractive therapeutic biotarget for T-cell and antibody-mediated autoimmune diseases. RegRF is anti-idiotypic antibodies that have a shared paratope in addition to an individual paratope. Epitopes specific to the shared regRF paratope (regRF epitopes) can be obtained on conformers of IgG Fc fragments. Immunization with Fc fragments carrying regRF epitopes reduces rat collagen-induced arthritis and diminishes experimental autoimmune encephalomyelitis. The aim of this study was to determine whether IgG Fc fragments bearing regRF epitopes suppress experimental autoimmune thyroiditis (EAT). Four weeks after EAT induction, rats were immunized with IgG Fc fragments exhibiting regRF epitopes. Histology studies of the thyroid were performed 4weeks later. Thyroid function and other parameters were also evaluated. Treatment of rats with Fc fragments bearing regRF epitopes decreased the number of rats affected by EAT, significantly decreased the extent of thyroid damage, prevented thyroid metaplasia, and restored normal thyroid hormone production. Therefore, RegRF is a promising biotarget in autoimmune thyroiditis, and Fc fragments bearing regRF epitopes are a potential therapeutic agent for that condition.

ODP299 Cabergoline Administration Markedly Improves Cognitive Impairment Associated with Macroprolactinoma

Abstract Introduction Prolactinomas classically present with galactorrhea, infertility, or hypogonadal symptoms. However cognitive impairment is rare presentation. We describe a man with a macroprolactinoma presenting with significant cognitive dysfunction which improved remarkably with cabergoline treatment. Case History A 21-year-old man with no significant past medical history presented to the hospital for evaluation of seizure-like activity. His father noted him limping earlier in the day and witnessed him fall and hit his head, while his brother reported involuntary convulsions and decreased awareness earlier that week. The patient himself had been complaining of blurry vision for 3 months for which he was prescribed glasses. Initial head CT demonstrated a 3.4×4.3×3.4cm cystic mass in the sella, 3.9×3.2×2.6 cm mass in the right basal ganglia and 2.7×2.3×3cm mass in the right temporal lobe. His prolactin was elevated at 16326 ng/mL. He was empirically started on dexamethasone due to concern for cerebral edema and was admitted. Surgery was recommended given the severity of his presentation, but the patient declined and he was discharged on cabergoline 1.5mg/week, dexamethasone taper, hydrocortisone 15mg/day, and levetiracetam 1000mg twice daily. On initial outpatient endocrinology evaluation 3 weeks later, he required the use of a wheel chair. Examination was notably for markedly flat affect, slurred speech, decreased attention span requiring frequent re-direction during the interview but he was otherwise oriented to person, time, and place. Neurological examination was noted for 4/5 muscle weakness throughout, facial asymmetry, decreased facial sensation, and an antalgic gait. He was recommended for expedited neurosurgical evaluation but he again declined. Laboratory drawn at this time showed a prolactin of 1946 ng/mL and total testosterone of 45 ng/dL, but he had normal thyroid and growth hormone axis (adrenal axis was not assessed as he was on dexamethasone taper). Carbergoline was titrated with further improvement in his prolactin levels. Four months after initial presentation, he reported enrolling in college with resolution of any cognitive and neurological deficits. Fourteen months after presentation, serum prolactin was 34 ng/mL on 4mg cabergoline per week and he is active in college and regularly plays basketball. Discussion Prolactinomas are incidentally detected or found as a result of workup for galactorrhea, infertility, or low libido. Typically, goals for treatment are to relieve compressive effects along the optic chiasm or to restore gonadal function. Acute cognitive decline should also be considered when there is a macroprolactinoma, and serial monitoring for improvement may be considered a clinical marker along with MRI imaging and prolactin levels. In this case, the patient had marked cognitive dysfunction on initial presentation but after 3 months of treatment had almost complete recovery as evidenced by his re-enrolling in college classes successfully. Presentation: No date and time listed

ODP387 Hemihypertrophy: A Rare Clinical Presentation of Cushing's disease

Abstract Background Hemihypertrophy is a rare clinical presentation of Cushing's disease. It has been described in three newborns with massive enlargement of adrenal glands in presence of other congenital abnormalities and in a 17-year-old female with pituitary adenoma with a genetic diagnosis of Beckwith Weidman syndrome. We describe a case of Cushing's disease with lower extremity hemihypertrophy in the absence of features suggestive of an underlying syndrome. 1,2 Clinical Case: A 12-year-old male with no significant past medical history presented with poor growth and rapid weight gain. In addition, he had hemihypertrophy of left lower extremity interfering with his physical activity. Physical exam showed Tanner Stage 1 for pubic hair and testicular volume of 4 ml bilaterally, with no signs of hirsutism, bruising or purplish striae. Initial work up showed normal thyroid hormone and growth factor levels. Midnight salivary cortisol levels were 238 ng/dl and 51 ng/dl respectively (range &amp;lt;100 ng/dl). One mg dexamethasone suppression test showed suppressed cortisol level of 1 mcg/dl. At the subsequent visit seven months later, he had gained 13.8 kg and grown 0.9 cm in height. Physical exam showed facial plethora and buffalo hump, which had not been present at the initial visit. Left and right leg circumference above the knee were 22 inches and 20 inches respectively. Repeat midnight cortisol levels on two separate occasions were 251 ng/dl and 441 ng/dl respectively. Repeat 1 mg dexamethasone suppression test showed suppressed cortisol levels of 1.2 mcg/dl. Because of clinical picture consistent with Cushing syndrome and elevated salivary cortisol levels, 24-hour urine cortisol levels were ordered that were 145 mcg and 276 mcg/24h respectively (range 1-45 mcg/24hours). ACTH was elevated at 65 pg/ml. CT scan of abdomen and pelvis was normal. Left leg ultrasound was normal. MRI of brain showed a 4 mm hypoenhancing lesion in the pituitary gland to the left of midline. A peripheral DDAVP stimulation test showed elevated ACTH and cortisol levels suggestive of pituitary origin. MRI of legs showed asymmetric fat deposition causing hemihypertrophy. Patient underwent transsphenoidal resection of pituitary adenoma with postoperative remission (postop cortisol nadir &amp;lt;1 mcg/dl). At follow up visit after surgery, patient had lost 0.2 kg, buffalo hump had disappeared, and left leg circumference had slightly improved. Genetic testing ispending. Conclusion This case demonstrates that hemihypertrophy can be a presenting symptom of Cushing's disease.

ODP079 BCG-Osis, a Rare Cause of 1,25 Hydroxy Vitamin D Mediated Hypercalcemia

Abstract Background Non-parathyroid hormone (PTH) mediated hypercalcemia is mostly related to malignancy and less commonly caused by granulomatous diseases. We report a rare case of severe hypercalcemia caused by systemic granulomatous disease after intravesical Bacillus Calmette-Guerin (BCG) treatment for bladder cancer (BCGosis). Clinical Case 74-year-old male with history of bladder cancer treated with intravesical BCG a year ago, was hospitalized with confusion, weakness, recurrent falls and polyuria for a few days. He had night sweats and 50 lb weight loss over 6 months. Lab evaluation showed hypercalcemia with calcium 10.9 mg/dL, albumin 3.6 g/dL, corrected calcium 11.2 mg/dL, PTH 12 pg/ml, and 25 OH vitamin D 44ng/ml. He had normal thyroid hormone levels, serum electrophoresis and PTHrP &amp;lt;2 pmol/L. CT chest/abdomen/pelvis without contrast revealed sub-cm pulmonary nodules and non-obstructive renal calculi and bone scan showed no evidence of osseous metastases. He was treated with intravenous (IV) hydration and pamidronate 60 mg infusion, and his corrected calcium improved to 9.7 mg/dL. He was admitted again 3 weeks later with hypercalcemia, calcium 11.9 mg/DL, albumin 3.2 g/dL, corrected calcium 12.5 mg/dL, 25 OH vitamin D 24 ng/ml, PTH 14.6 pg/ml, and PTHrP &amp;lt;2 pmol/L. He received IV hydration and zoledronic acid 4 mg infusion. 3 weeks later he was hospitalized for the third time for recurrent hypercalcemia and worsening renal failure, calcium 13.2, albumin 2.6 g/dL, corrected calcium 14.2 mg/dL, PTH 19.2 pg/ml. 1,25 OH vitamin D checked this time was elevated at 113 pg/mL. He received another infusion of zoledronic acid 4 mg infusion and 10 days later required denosumab 120 mg for resistant hypercalcemia. PET CT scan showed multiple hypermetabolic foci in right neck, right anterior 4th rib, scrotum, and around left kidney and aorta. He underwent biopsy of the right rib lesion which demonstrated + AFB on smear and histiocytic inflammation, which led to diagnosis of BCGosis, with subsequent cultures positive for Mycobacterium bovis. He was started on multi drug regimen with rifampin, isoniazid and ethambutol. Follow up labs at 4 weeks showed normalization of calcium 8.9 mg/dL, albumin 3.2 g/dL, corrected calcium 9.78 mg/dL, PTH 54 pg/ml and low 1,25 OH vitamin D 17 pg/mL. Calcium and 1,25 OH vitamin D levels were stable at 4 months follow up. Conclusion Intravesical BCG treatment can be associated with systemic reactions in 1- 5% of patients. Granulomas associated with disseminated BCG infection can lead to hypercalcemia due to increased 1-alpha-hydroxylase activity in macrophages, causing elevated 1,25 OH vitamin D levels. Therefore, evaluation of 1,25 OH vitamin D levels is critical to determine the etiology of hypercalcemia. Treatment of underlying BCGosis with anti-tuberculosis treatment is key in management of hypercalcemia along with supportive treatments that may include IV hydration, bisphosphonates and/or glucocorticoids. Presentation: No date and time listed