Biochemical Workup Research Articles

Identification of a Novel CYP11B2 Variant in a Family with Varying Degrees of Aldosterone Synthase Deficiency

Isolated aldosterone synthase deficiency is a rare autosomal recessive disorder caused by pathogenic variants in CYP11B2, resulting in impaired aldosterone synthesis. We report on a neonate with isolated aldosterone synthase deficiency caused by a novel homozygous CYP11B2 variant Chr8:NM_000498.3:c.400G>A p.(Gly134Arg). The patient presented shortly after birth with severe signs of aldosterone deficiency. Interestingly, segregation analysis revealed that the patient's asymptomatic father was also homozygous for the CYP11B2 variant. Biochemical evaluation of the father indicated subclinical enzyme impairment, characterized by elevated aldosterone precursors. Apparently, this homozygous variant led to different clinical phenotypes in two affected relatives. In this manuscript we elaborate on the performed biochemical and genetic work-up and describe potential pitfalls of CYP11B2 sequencing due to its homology to CYP11B2.

2D Shear Wave Elastography, a promising screening tool for Cystic Fibrosis liver disease, shows a correlation between vitamin D and liver stiffness

BackgroundLiver disease in Cystic Fibrosis (CFLD) is an early complication of CF. Evidence of CFLD is often subclinical and screening is recommended. Screening includes a biochemical work-up and an ultrasound investigation. Non-invasive methods measuring liver stiffness such as shear wave elastography could be beneficial. This study describes the use of 2D Shear Wave Elastography (2D SWE) in screening for CFLD in a clinical setting and explores its correlation to other indicators of CFLD. Furthermore, a relationship between liver stiffness and nutritional status, lung function and glucose tolerance was explored. Material and MethodsA retrospective cohort study was performed at a pediatric CF center. Information was gathered from the patients’ charts and the Swedish national CF registry. The patients included had been evaluated for the presence of CFLD by ultrasound and 2D SWE during 2018-2020. Demographic data as well as data concerning nutritional status, lung function and glucose tolerance were collected. ResultsFifty-one subjects were included with a median age of 11 years. Four children who had biopsy confirmed liver cirrhosis had significantly increased liver stiffness. There was a statistically significant negative correlation between liver stiffness and vitamin D levels and FEV1% predicted respectively. Children with abnormal glucose tolerance had increased liver stiffness compared to their normal glucose tolerant counterparts. ConclusionMeasuring liver stiffness by 2D SWE is a reliable addition to CFLD screening with data comparable to the more conventional ultrasound investigation. Increased liver stiffness is associated with lower vitamin D levels, lower FEV1% predicted and abnormal glucose tolerance.

Clinical Profile and Outcome in Patients of Complicated Urinary Tract Infections: A Single-Center Prospective Observational Study.

BackgroundComplicated urinary tract infection (cUTI) is the one which is associated with structural and functional abnormalities of the urinary tract, thus increasing the risk of infection and failure of therapy.Aim:This study aims to determine the risk factors, changing trends in etiology, current treatment options, and outcomes in cUTI.Materials and Methods:This prospective observational study was done on patients presenting with cUTI. Hematological, biochemical workup, urine routine, urine culture, blood culture, ultrasonography, and wherever necessary computerized tomography of the genitourinary tract was done. The medical/surgical interventions and outcomes in these patients were recorded.Results:A total of 100 patients were enrolled in the study. Diabetes mellitus was the most common risk factor present in 53%. The most common organism isolated in urine culture was Escherichia coli (48%) followed by Klebsiella pneumoniae (19%) and similar trend but lesser positive yield was there in blood culture (Escherichia coli - 26% followed by Klebsiella pneumoniae - 3%). The organisms were most susceptible to colistin/polymyxin (100%) followed by carbapenems (88%), and later were the most commonly used empirical antibiotics in our study, yielding 95% survival rate. Surgical interventions (percutaneous/endourological) were required in 28%, renal replacement therapy in 14%, intensive care in 40% and mechanical ventilation in 10%, with 4% overall mortality at the end of 1-month follow-up. The mean duration of hospital stay was 9.1 ± 2.7 days.ConclusionEscherichia coli was the most common organism causing cUTI, with diabetes being the most common risk factor. Most of the patients were treated with carbapenems with excellent survival outcomes.

Response of Patients with Acromegaly to Long-acting Octreotide with regard to Regression of Pituitary Adenoma, Growth Hormone and Insulin-like Growth Factor-1

Introduction: Acromegaly is a rare endocrine disease; its treatment is surgical (Hypophysectomy). However, somatostatin analogs represent another modality of therapy in addition to deep X-ray therapy as a third, option. The aim of the study is to find out the response of patients with acromegaly to octreotide as reflected on regression of adenoma size, insulin-like growth factor (IGF), and growth hormone (GH) by studying the medical records of many patients with acromegaly. Method: A total of 80 patients with acromegaly are enrolled in the study from July/2019 to April/2020. Their age range (20–72 years). They are 47 men and 33 women. Their selection was based on their visits to NDC on the basis of prescheduled appointments to be given their monthly injections of long-acting octreotide (LAR) and to be examined clinically plus conducting various types of hormonal studies and biochemical workups to assess their response to treatment on the following parameters: Adenoma size, IGF-1 and GH and its correlation with octreotide dose. Results: It is a cross-sectional comparative clinical trial study of 80 patients with acromegaly. Mean of age was 46.7 ± 12.4 years’, and their age range (20–72 year) minimum and maximum-year-old. Mean duration of taking drug was 8 ± 6.7 years. The mean of total LRA injection was (1073.6 ± 666.2 mg). 58.75% of patients were male while 41.25% were female. 46.25% of patients do not have transsphenoidal direct surgery, but 46.25% undergo one surgery, 7.5% undergo two transsphenoidal hypophysectomies. 87.5% of patients have no gamma knife while 12.5% have gamma knife radiosurgery. Conclusion: Acromegaly is a multi systemic disease that should be diagnosed and treated as early as possible to prevent complications and improve mortality rates.

CHANGES IN RETINAL VESSEL DIAMETER ARE ASSOCIATED WITH CEREBRAL MICROBLEEDS IN NEUROLOGICALLY ASYMPTOMATIC INDIVIDUALS WITH TYPE 1 DIABETES

Objective: We observed recently that a third of asymptomatic individuals with type 1 diabetes (T1D) showed signs of cerebral small-vessel disease in brain magnetic resonance imaging (MRI). Here, we aimed to explore the relationship between an easily applicable quantitative measure of retinal vessel diameters (RVD) and cerebrovascular changes in these individuals. Design and method: We included 188 individuals with type 1 diabetes and 30 healthy sex and age matched (49% males, median age 40 years) controls. Any neurological signs or symptoms were exclusion criteria. All subjects underwent a clinical and biochemical work-up, as well as brain MRI. Both retinas were phenotyped by measuring the width of all vessels located 0.5 to 1.0 disc diameters from the disc margin by a computer-assisted method (IVAN software). Summarized estimates for central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) represented average retinal vessel diameters. The arteriole-to-venule ratio (AVR) was calculated as an additional estimate of early retinal vascular pathology. Associations between blood pressure (BP), cerebral microbleeds (CMBs), white-matter hyperintensities (Fazekas classification), and CRAE, CRVE, and AVR were assessed with non-parametric tests and linear regression models. Results: No difference in CRAE, CRVE, or AVR were found between individuals with type 1 diabetes and controls. An expected correlation between BP and CRAE (p = 0.01) was observed. Median AVR was lower among individuals with T1D and cerebral microbleeds (p = 0.02) compared to those without. A correlation between AVR and the number of CMBs (p = 0.035) was also found. Further, median CRAE was lower among those with > 10 CMBs (p = 0.039) compared to those without. We observed no correlations between RVD and white-matter hyperintensities. Conclusions: Individuals with CMBs had lower CRAE and AVR suggesting that early vascular changes in the retinal are indicative of cerebrovascular pathology in middle aged individuals with T1D.

PREDICTION OF ESOPHAGEAL VARICES IN COMPENSATED CHRONIC LIVER DISEASE PATIENTS BY USING FIBROSCAN, SPLEEN SIZE AND PLATELET COUNT

Background - In this study, we aim to identify the noninvasive methods like Fibroscan, spleen size, platelet count, and their combinations in correlating and predicting esophageal varices. Methods - This observational study includes patients diagnosed with Compensated Chronic liver disease presented for the rst time. Relevant physical examination and clinical parameters were assessed, including complete hemogram, biochemical workup, liver stiffness using Fibroscan, USG measurement of spleen long axis diameter, Upper GI endoscopy for variceal screening, and grading. Results – A signicant correlation between platelet count and the presence of varices was noted (P<0.001), with a cut-off count of 150 x 109/L, with a sensitivity of 88.9% and a specicity of 97.2%, And for high-risk varices the optimal Cut-off was 128 x 109/L. The Cut-off point for Spleen diameter for the presence of varices was 14.15cm with 94.7% sensitivity and 84.1% specicity with a signicant pvalue < 0.001. High-risk varices optimal Cut-off was 14.65cm. Similarly, the best cut-off point for liver stiffness and the presence of varices was 21kPa, with a sensitivity of 96.0% and a specicity of 97.4% with a signicant p-value < 0.001, and for high-risk varices was 25.5kPa. A statistically signicant correlation was observed between the Liver stiffness spleen diameter platelet score (LSPS) in predicting varices and highrisk varices with the best cut-off value of 2.05 and 3.11, respectively Conclusion - Our study concludes that Fibroscan, Spleen Size, and platelet count, individually and Combined LSP Score is a valuable tool in predicting the presence of esophageal varices and severity. From all these parameters, we could identify the subset of patients who require endoscopy screening for esophageal varices.

Diagnosis and management of the metabolic syndrome with pulmonary and liver diseases

Introduction: The metabolic syndrome is a condition characterized by a cluster of alterations including glucose intolerance/ insulin resistance, abdominal obesity, atherogenic dyslipidemia (low concentrations of high-density lipoprotein-cholesterol and high concentrations of triglycerides), elevated blood pressure, a proinflammatory and a prothrombotic state. It increases morbidity and mortality, especially due to cardiovascular disease. Material and Method: This study has been performed in 90 consecutive patients referred to our metabolic outpatient clinic for suspected metabolic disorders. This study conducted among patients attending at Tertiary care teaching hospital over a period of 1 year. Patients underwent a complete clinico-pathology and biochemical work-up, including a liver ultrasonographic scanning (US), as part of the routine clinical examination. MetS was defined by a combination of abdominal obesity, impaired fasting glucose, atherogenic dyslipidemia, and elevated blood pressure. Results: A total of 90 participants (53 males) were included in the study. The characteristics of the eligible subjects stratified by gender and the presence of metabolic syndrome. The BMI, SBP, DBP, waist circumference was statically significant between male and female (all of the parameters, p<0.05).

Review of MIS-C Clinical Protocols and Diagnostic Pathways: Towards a Consensus Algorithm.

BackgroundThe emergence of multisystem inflammatory syndrome in children (MIS-C) during the severe acute respiratory syndrome coronavirus 2 pandemic led to the development of institutional clinical pathways based on expert opinion. We assessed North American paediatric centres’ adaptation to MIS-C and analysed the degree of agreement between algorithms on tiered clinical investigations.MethodsThis study evaluated MIS-C diagnostic algorithms from 50 tertiary centres developed between May 2020 and December 2021 in the United States and Canada obtained online and through colleagues in various institutions. Descriptive statistics were used to analyse results.ResultsAll clinical pathways used a tiered approach, and most required coronavirus disease 2019 polymerase chain reaction testing on presentation. Over one-quarter used a 24-hour fever to initiate investigations, and another quarter used 3 days. Basic biochemical workup was performed in all centres on presentation (complete blood count, inflammatory markers, hepatic, and renal functions). Specialized investigation was generally reserved for secondary testing (cardiac biomarkers, electrocardiogram and echo, and coagulation panel). Institutions were divided on several investigations for tier distribution, including urine studies, blood cultures, chest radiograph, and severe acute respiratory syndrome coronavirus 2 serology. Subspecialty consultations were reserved for second-line testing, including cardiology, infectious disease, and rheumatology. Finally, we propose a composite algorithm representative of the consulted pathways.ConclusionsFaced with an unprecedented clinical challenge, paediatric institutions responded swiftly with evaluation standardization, adapting to evolving knowledge. Most pathways agreed on initial basic screening tests followed by secondary workup including cardiac investigations. These protocols, developed during a high level of uncertainty, require comparative assessment on efficacy and superiority.

The putty kidney: a classic sign from past in genitourinary radiology.

A 56-year-old woman with known genitourinary tuberculosis (GUTB) presented for follow-up evaluation with Computed Tomography (CT). Her urine referred acidic with few pus cells, but sterile on culture. Other laboratory tests were normal. A pigtail catheter is also referred to the left kidney. X-ray (actually CT-topogram) kidney, ureter and bladder (KUB) show multiple lobulated calcifications in the right renal region conglomerated into the shape of the kidney. This imaging finding were suggestive of the classical “putty kidney sign” of an end stage renal tuberculosis (TB). Radiological findings in renal TB depend on the extent of the disease process and are best demonstrated both on intravenous urogram and CT scan. Describing the condition, it is an extensive parenchymal calcification in a non-functioning kidney, forming its cast. The “putty kidney” or “autonephrectomy” is the end result of scarring, obstruction, and atrophy of the kidney due to TB which is complicated by dystrophic calcification with time. Tuberculosis of the kidney results from hematogenous seeding of M tuberculosis in the glomerular and peritubular capillary bed from primary pulmonary infection. Disease´s physiopathology and/or progression includes granuloma formation which causes necrosis with cavitation within the renal parenchyma, fibrosis, calcium deposition and stricture formation. Diagnosis of GUTB based on biochemical workup is often delayed and high index of suspicion required to avoid misdiagnosis. Thus, imaging has an important role in diagnosis. The present X-ray KUB and CT is a classic example of such “putty kidney” which first described in 1906 by Dr. F.Tilden Brown, a genitourinary surgeon (Figure 1).

Clinical presentation and surgical resolution of atypical non-adenomas adrenal tumors

Adrenal tumors are very common in medical practice, including a wide spectrum of etiologies. Although most of them are adenomas, infrequent lesions can become a diagnostic and therapeutic challenge for clinicians. Here we present two atypical cases of non-adenomas adrenal tumors with specific imaging, biochemical profile, and surgical resolution. The first case is a 54-year-old woman with a history of hypertension and type 2 diabetes, with an incidentally discovered 7 cm adrenal mass on CT, compatible with a myelolipoma. Biochemical work-up was remarkable for hypersecretion of both cortisol and aldosterone. She underwent laparoscopic adrenalectomy. During follow-up, biochemical cure of hormonal hypersecretion was confirmed. The second case is a 44-year-old woman in whom a 7 cm left non-adenoma adrenal mass was diagnosed incidentally by magnetic resonance. Complete hormonal screening was normal. Laparoscopic adrenalectomy was performed. Biopsy informed a solid neoplasm separated from normal adrenal tissue, with immunohistochemistry compatible with a Schwannoma. These case vignettes describe atypical adrenal cases that should be considered in the differential diagnosis of non-adenomas adrenal tumors. They represent uncommon presentations and illustrate the importance of an appropriate multidisciplinary evaluation of adrenal tumors, in order to improve the surgical and clinicalmanagement of these patients. Keywords: adrenal incidentaloma; adrenal tumor; adrenal myelolipoma; adrenal schwannoma.

A case of Graves' disease and type 1 diabetes mellitus following SARS-CoV-2 vaccination

Autoimmune diseases, including autoimmune endocrine diseases (AIED), are thought to develop following environmental exposure in patients with genetic predisposition. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and vaccines against it could represent new environmental triggers for AIED. We report a patient, with history of vitiligo vulgaris and 8 years of type 2 diabetes, who came to our institution because of fever, weight loss, asthenia and thyrotoxicosis occurred 4 weeks later the administration of BNT162B2 (Pfizer-BioNTech) SARS-CoV-2 vaccine. Clinical, biochemical and instrumental work-up demonstrated Graves’ disease and autoimmune diabetes mellitus. The occurrence of these disorders could be explained through different mechanism such as autoimmune/inflammatory syndrome induced by adjuvants (ASIA syndrome), mRNA “self-adjuvant” effect, molecular mimicry between human and viral proteins and immune disruption from external stimuli. However further studies are needed to better understand the underlying pathogenesis of AIED following SARS-CoV-2 vaccine.

Ectopic Parathyroid Adenoma Mimicking as a Neuroendocrine Tumor on Ga68- DOTANOC Positron Emission Tomography/Computed Tomography Imaging.

Parathyroid adenoma sometimes present in ectopic location and may pose a difficulty in both diagnosis and localization. We report a case of a young lady suspected to have neuroendocrine tumor of the mediastinum demonstrating synaptophysin positivity on an initial core needle biopsy. Ga-68 DOTANOC positron emission tomography–computed tomography revealed a somatostatin receptor-expressing lesion in the anterior mediastinum with tracer avid multiple lytic bone lesions. On further biochemical and imaging workup with Tc-99 m SESTAMIBI, a diagnosis of ectopic parathyroid adenoma was made which was further confirmed with surgical excision.

New developments and perspectives in acromegaly

Acromegaly is a rare but severe disorder which is usually due to an excessive secretion of growth hormone (GH) by a pituitary adenoma. Screening mainly relies on the measurement of insulin-like growth factor 1, and confirmatory diagnostics includes a GH suppression test. As delayed diagnosis results in increased morbidity and mortality, we here discuss recently published suggestions regarding the biochemical work-up of suspected cases and the follow-up of co-morbidities. Moreover, new analytical tools (such as automatic identification of typical facial changes using artificial intelligence) are presented, hopefully allowing for an earlier diagnosis in the future. So far, surgery is still regarded as therapy of first choice. In cases without postoperative remission, a new imaging approach (combining sellar magnetic resonance imaging and position emission tomography) may improve the results of repeated surgery. The pharmaceutical arsenal now includes the first orally available somatostatin analogue, and recent data on possible drug combinations and the outcome of radiotherapy are presented. Finally, special attention is paid to older and pregnant patients, as well as certain considerations during the COVID-19 pandemic (where appropriate diagnosis and management of acromegaly is particularly challenging).

A Novel, Likely Pathogenic MAX Germline Variant in a Patient With Unilateral Pheochromocytoma.

ContextInherited MYC-associated factor X (MAX) gene pathogenic variants (PVs) increase risk for pheochromocytomas (PCCs) and/or paragangliomas (PGLs) in adults and children. There is little clinical experience with such mutations.ObjectiveThis report highlights an important approach.MethodsClinical assessment, including blood chemistry, imaging studies, and genetic testing were performed.ResultsA 38-year-old Hispanic woman was diagnosed with PCC in 2015, treated with adrenalectomy, and referred to endocrinology clinic. Notably, she presented to her primary care physician 3 years earlier complaining of left flank pain, intermittent diaphoresis, and holocranial severe headache. We confirmed severe hypertension (180/100 mm Hg) over multiple antihypertensive regimens. Biochemical and radiological studies workup revealed high plasma metanephrine of 255 pg/mL (normal range, < 65 pg/mL) and plasma normetanephrine of 240 pg/mL (normal range, < 196 pg/mL). A noncontrast computed tomography scan of the abdomen revealed a 4.2 × 4.3 × 4.9-cm, round-shaped and heterogenous contrast enhancement of the left adrenal gland, and a 2-mm nonobstructive left kidney stone. A presumptive diagnosis of secondary hypertension was made. After pharmacological therapy, laparoscopic left adrenalectomy was performed and confirmed the diagnosis of pheochromocytoma. Based on her age, family history, and a high suspicion for genetic etiology, genetic testing was performed that revealed the presence of a novel likely pathogenic variant involving a splice consensus sequence in the MAX gene, designated c0.64-2A > G.ConclusionThe phenotype of MAX PV-related disease and paraganglioma are highlighted. The novel c0.64-2A > G mutation is reported here and should be considered in the diagnostic workup of similar cases.

Second wave of COVID-19 pandemic and the surge of mucormycosis: Lessons learnt and future preparedness: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement.

Second wave of COVID-19 pandemic and the surge of mucormycosis: Lessons learnt and future preparedness: Indian Society of Anaesthesiologists (ISA National) Advisory and Position Statement.

Multifocal pancreatic PPoma in the setting of MEN1: Case report and review of literature.

Introduction and importanceFunctioning pancreatic neuroendocrine tumors (pNETs) that express pancreatic polypeptide—PPomas—do not yet have a pathognomonic clinical syndrome associated with them due to their overall rarity and diverse symptoms. Moreover, in patients with MEN1, the often multifocal nature of pNETs presents a unique clinical issue.Case presentationWe report a case of a 22-year-old man with a known MEN1 gene mutation who was suffering from severe diarrhea (7–8 bowel movements per day) and was found to have only elevated PP levels on biochemical work-up. Ga68-DOTATATE PET/CT showed multifocal tumors in the body and tail of the pancreas that were not evident on contrast-enhanced CT. The patient underwent a successful laparoscopic radical antegrade modular pancreatosplenectomy (RAMP) and recovered well post-operatively with complete resolution of his diarrhea. Immunohistochemistry showed multiple pure PPomas.Clinical discussionThis case highlights the unique propensity for multifocal disease in patients with MEN1 mutations and the utility of functional imaging by somatostatin analogs, i.e., Ga68-DOTATATE PET/CT, in order to perform oncologic laparoscopic pancreatic resections.ConclusionPPomas in the setting of MEN1 mutations are a unique clinical entity due to their diverse associated clinical syndromes and propensity for multifocal disease.

Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome

Background: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE. Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE. Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred >3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P < 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS. Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis.

Hyperthyroidism Times 2: Dual Cause of Thyroid Hormone Excess

The most common etiology of Hyperthyroidism is due to circulating antibodies that are directed against the thyroid-stimulating hormone (TSH) receptor, known as Grave’s Disease (GD). Another cause is an autonomously functioning thyroid nodule over-producing hormones or Toxic Adenoma. The mechanism of these two pathologies are very distinct, but the question that arises is, can they coexist?This is a case of 44-year-old female who comes to the clinic referred by her ophthalmologist after been diagnosed with severe thyroid-associated orbitopathy currently on steroid therapy. Thyroid ultrasound has done previously showed enlarged homogenous thyroid gland with a single isoechoic nodule of 2.2x1.6x1.9cm with faint peripheral calcifications and vascularity. The patient was presenting with palpitations, heat intolerance, sweating, and discriminatory features such as double vision and left eye exophthalmos. On physical examination, there was no goiter or palpable thyroid nodules, but it was remarkable for left eyelid lag retraction and mild proptosis. Evaluation showed clinical and biochemical hyperthyroidism with TSH: 0.068 mU/ml (n:0.5-5.0mU/ml), FT4: 1.39ng/dl (n:0.87-1.85ng/dl), TSH receptor antibody: <1.10IU/L and thyroid-stimulating immunoglobulin: 0.54IU/L (borderline high). The patient was placed in antithyroid drugs and B-blockers for disease control. Afterward, the patient underwent a thyroid uptake scan reporting toxic adenoma on the left lobe, however even when the biochemical workup of GD is inconclusive, patient clinical findings are highly suggestive of it. Due to the risk of worsening orbitopathy with radioactive iodine therapy, patient was referred for surgical excision of toxic adenoma and total thyroidectomy was decided since residual thyroid tissue may expose the patient to circulating thyroid-stimulating immunoglobulin leading to hyperthyroidism recurrence and put her at risk of associated thyroid excess detrimental complications. Surgical specimen gross pathology biopsy reported the thyroid gland with hyperplastic changes of Grave’s Disease. Severe thyroid-associated orbitopathy was managed with decompression surgery but did not improve, for which an alternative therapeutic approach is decided with novel immunomodulatory agent and recent approved therapy, Teprotumumab. A monoclonal antibody that works on TSHR/IGF-1R signaling complex involved in Thyroid Eye Disease.Is unusual to see two different superimposing thyroid pathologies, but disease presentations can be atypical and can be present concomitantly. In this scenario, several factors must be taken into consideration when choosing an adequate therapy approach. Our case is an example that we need to individualize management options based on guidelines recommendations, patient’s clinical settings and decreased risks of future complications.

Transaminitis Evaluation Leads to the Incidental Diagnosis of Familial Paraganglioma Due to SDHB Mutation

Background: Paragangliomas are rare neuroendocrine tumors. Patients with succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. We are presenting the case of an incidental finding of a paraganglioma during an evaluation for transaminitis. Clinical Case: A 23-year-old male with a medical history of right hydrocele repair as a teenager was evaluated with an ultrasound of the abdomen for elevated liver enzymes and right upper quadrant discomfort. The ultrasound revealed a large lobular solid vascular 13.8 x 8.1 x 11.3 cm mass in the mid abdomen. He underwent a CT of the chest, abdomen and pelvis which demonstrated a large retroperitoneal mass measuring 16 x 10 x 13.7 cm within the right mid abdomen. The mass was described as a large centrally necrotic peripherally enhancing right retroperitoneal mass displacing the IVC anteriorly. The patient subsequently underwent an image-guided biopsy of the mass and the pathology revealed it was a paraganglioma. The patient denied any history of hypertension, orthostasis, headaches or palpitations. Biochemical workup for plasma catecholamines, plasma metanephrines, 24-hour urine catecholamines and metanephrines and cortisol were unremarkable. His transaminitis also resolved. He underwent a retroperitoneal paraganglioma excision and the final pathology was consistent with paraganglioma and negative for capsular invasion. He was referred to a genetic counsellor for testing since paragangliomas can be inherited. He also mentioned a family history of breast cancer in his mother and HTN and prostate cancer in his father. His test revealed that he had a c.289A>T mutation in his SDHB gene. He was encouraged to share the information with his family to help them understand the implications of his genetic test result. He underwent a surveillance PET scan which showed multiple osseous lesions in his temporal calvarium, sphenoid, spine and sacrum suggestive of metastasis. Repeat imaging with a DOTATATE PET scan showed stable disease. His transaminitis was transient, and we did not find a correlation to his paraganglioma. His imaging tests showed no liver metastasis. A CT of the head showed no evidence of intracranial metastasis. The current plan is to continue surveillance. His older brother underwent a genetic testing. He tested positive for the same SDHB mutation and underwent biochemical and imaging tests which were unremarkable. He too will continue surveillance. Conclusions: Patients with a succinate dehydrogenase subunit B (SDHB) gene mutations are predisposed to developing paraganglioma/pheochromocytoma. The tumors produce catecholamines, but can be biochemically silent as in our patient. They are inherited in an autosomal dominant manner. Our case highlights the importance for genetic counseling which increases the chances of early screening and surveillance in affected family members for optimal multidisciplinary management of patients.

Presentation of ACTH Independent Cushing’s as Severe Insulin Resistance During Pregnancy

Introduction: Cushing’s syndrome is very rare in pregnancy with around 200 cases reported in literature. It remains a diagnostic dilemma as pregnancy itself is a hypercortisolemic state. Several clinical characteristics of Cushing’s syndrome such as insulin resistance and hirsutism may overlap with normal variants of pregnancy and therefore leading to a missed diagnosis. We hereby present a case of a young pregnant woman with severe insulin resistance, with workup consistent with Cushing’s syndrome. Clinical Case: This was a 27-year-old pregnant woman with DM type 2 diagnosed about 7 years ago. During her pregnancy she was started on insulin and was later admitted to the hospital at 32 weeks for inpatient management of pre-eclampsia and uncontrolled hyperglycemia. Endocrine was consulted for severe insulin resistance and persistent hyperglycemia. On exam patient was noted to be obese with facial plethora, frontal balding and significant facial hirsutism. During the pregnancy she had noted significant weight gain with substantial worsening of frontal balding and hirsutism. Her current pregnancy was spontaneous but was after many years of trying to conceive. Prior pregnancy 8 years ago was uncomplicated with no history for GDM at that time. Review of recent pre-pregnancy imaging revealed left adrenal mass measuring 3.5 cm with 40 HU which measured around 2 cm 8 years ago. Biochemical work up revealed elevated 8 am cortisol at 35.4 ug/dL (ref range 6.2 - 19.4) with suppressed ACTH <5 pg/mL (6 – 50). Testosterone was high at 299 ng/dL (8 – 48) and DHEAS was low normal at 37 mcg/dL (18 – 391). Plasma and 24 hour urine metanephrine collection results were normal. 24-hour urine free cortisol was measured and was elevated at 628.5 mcg/24(4.0–50.0). Midnight salivary cortisol was 0.87 mcg/dL (<OR=0.09). Patient was managed conservatively with plan for surgical intervention post-delivery. Pregnancy was complicated by PPROM at 35 weeks with subsequent cesarean section. Baby was of average weight but developed mild hyperbilirubinemia which required short NICU stay. On reevaluation at 4-week postpartum period, repeat biochemical workup revealed elevated cortisol of 22.5 mcg/dL, ACTH <5 pg/ml, elevated 24-hour urine cortisol 163.9 mcg/24h with appropriate urinary creatinine. Testosterone level was improved postpartum to 9 ng/dL. DHEAS was 39 mcg/dL. Repeat imaging with CT with adrenal protocol revealed left adrenal mass measuring 2.3 cm with 20 HU with absolute washout of 79%. She was started on ketoconazole is now awaiting surgical intervention. Conclusion: We suspect that this patient may have had pregestational subclinical Cushing’s syndrome which eventually progressed to Cushing’s syndrome during pregnancy. Although this is a rare finding during pregnancy, workup for Cushing’s should be considered in pregnant women with severe insulin resistance, hirsutism, hypertension and pre-eclampsia.