Cushing’s syndrome (CS) is considered a rare disease. The most common cause is the exogenous use of glucocorticoids (GCs), which are often given within a controlled medical setting, but their factitious use is rare. Factitious CS is more common in females, young patients, those with psychiatric disorders, and those with contacts within the medical field. The diagnosis of CS is challenging because some features are non-specific and commonly present in the general population, such as obesity, depression, diabetes, hypertension (HTN), and low bone mineral density (BMD). A high suspicion is warranted. We present the case of a 47-year-old man with HTN, obesity, dyslipidemia, obstructive sleep apnea, and low BMD who complained of increased appetite, significant weight gain, fatigue, sleepiness, muscle weakness, and occasional facial flushing. Medications include Hydrochlorothiazide, Furosemide, Losartan, Atorvastatin, and Teriparatide. Vital signs were normal and body mass index was 41.9 kg/m2. He had a round face, central obesity, and wide purple striae in his abdomen. Dual-energy X-ray absorptiometry scan showed low BMD at spine. Laboratories revealed a glycated hemoglobin of 6.1%, late-night salivary cortisol of <0.03 mcg/dL, 24-hour urine free cortisol of 22.5 mcg/24hr, morning cortisol of 0.01 ug/mL, ACTH 23.5pg/mL, and dehydroepiandrosterone sulfate (DHEA-S) 35 mcg/dL. Our patient persistently denied use of exogenous GCs, but a urine synthetic GC screen disclosed a positive result for dexamethasone; levels at 1.1 mcg/dL. After an exhaustive conversation, our patient confessed to using over-the-counter dexamethasone 4mg to treat occasional muscle aches. ACTH is usually suppressed in factitious CS, but this was not our patient’s case, giving the appearance of ACTH-dependent hypercortisolism. This can lead to unnecessary diagnostic and therapeutic approaches. An unsuppressed ACTH could be due to an unreliable ACTH immunoassay or intermittent, instead of continuous, ingestion of GCs. A suppressed DHEA-S level, as seen in our patient, may provide the clue to exogenous GC use as the cause of CS. Our case is also rare because our patient is male, older, and not related to the medical field. Hypercortisolism must be detected and treated early due to its high morbidity and mortality. Several features may be reversed with treatment. The possibility of hypothalamic-pituitary-adrenal (HPA) axis suppression due to prolonged use of GCs, resulting in adrenal insufficiency (AI) should be considered. The prevalence of GC-induced AI ranges from 14–63%, with the highest risk in those with Cushingoid features and those receiving a dose equivalent to prednisone 20mg daily for more than three weeks. Sudden withdrawal of GCs should be avoided to prevent adrenal crisis. A tapering regimen should be adopted with subsequent biochemical testing of the HPA axis once GCs have been reduced to a physiologic dose.

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.

Thyroid Nodules: Not So Simple to Manage Thyroid nodules diagnosis and malignancy risk stratification remains a challenge for decision making between conservative vs invasive management. The development of the clinical guidelines provides alternatives for evaluation and management for thyroid nodules, but can be used for all patients? A 43 y/o female without known past medical history is referred to the endocrine service by her primary care physician for evaluation of a thyroid nodule. She was presenting with 1 month history of mild discomfort on the neck and was evaluated with thyroid US that was relevant for multiple bilateral solid nodules measuring <1.0cm and a one spongiform measuring 1.7 x 1.2 x 1.3cm in the right lobe extending minimally to the capsule laterally and to the carotid artery wall. Patient denies cough, hoarseness, odynophagia, shortness of breath, family history of thyroid cancer or radiation exposure. On examination there were no goiter nor palpable thyroid nodules, as well as no clinical signs and symptoms of thyroid disease. Patient is clinically and biochemically euthyroid with a very low suspicion thyroid nodule (3% estimated malignancy risk). Despite nodule is below the 2.0cm cutoff point for fine needle aspiration biopsy (FNAB) according to American Association of Clinical Endocrinologist (AACE) and American Thyroid Association (ATA) guidelines, it was done based on additional suspicious sonographic features detect by the endocrinologist on evaluation of ultrasound images. FNAB was performed and reveals Atypia of undetermined significance/Follicular Lesion of undetermined significance (AUS/FLUS) Bethesda system category III with a risk of malignancy of 5–15%. Patient was reluctant to surgery given the very low risk nodule and biopsy results of AUS/FLUS. In order to further manage this patient with undetermined significance thyroid nodule, Gene Expression Classifier (GEC) Molecular Analysis (AFIRMA) was performed. AFIRMA test was done with a second FNAB that also reveals AUS/FLUS but was found positive for BRAFv600, Bethesda system category IV: Suspicious of Papillary Thyroid Carcinoma. BRAFv600 is the only mutation that have high specificity (99%) for papillary thyroid carcinoma and is associated with increased disease-specific mortality, aggressive histologic phenotypes, lymph node metastases, extrathyroidal extension and risk of recurrence. Based on this data patient now have 95% risk of malignancy and requires surgical therapy. Patient preferred total thyroidectomy over lobectomy; pathology results shows 2.0cm Papillary Thyroid Carcinoma Stage I (T1N0M0). Despite very low risk nodule finding, malignancy was diagnosed. As depicted in this case, thyroid nodules aren’t so simple to manage, and their management should involve imaging and pathology findings along with clinical judgement and patient individualization in decision making process.

Introduction: Human Regular U-500 Insulin is used to control high blood glucose in diabetic patients who need more than 200 units of insulin daily. High-dose insulin therapy may be limited because the volumes of insulin necessary to achieve these very high doses are difficult to administer subcutaneous and there is a decrease in the absorption rate. We report a case of a woman with DM2 and severe insulin resistance who achieved glycemic control using off-label U-500 via continuous subcutaneous insulin infusion (CSII) but with fixed bolus given manually by patient and remained controlled over the next six years. Clinical Case: A 66-year-old woman with DM2, HTN, metabolic syndrome and adiposity based chronic disease referred to endocrinologist office for glycemic control. Patient treated for diabetes with metformin and premixed insulin and HTN treated with CCB/ACE inhibitor and beta blocker/thiazide combinations. Clinical examination reveals an obese female (BMI: 37.9kg/m2) with acanthosis nigricans. Initial laboratory test showed HbA1c of 13.9%, FBS 293mg/dL, cholesterol 195mg/dL, TGs 147mg/dL and LDL 103mg/dL. Patient was treated with multiple insulin regimens, including U-500 insulin by subcutaneous route of administration and oral antihyperglycemic agents including followed up by nutritionist, where the lowest HbA1c was 9.1%. Patient total daily dose of insulin was 220 units. Although U-500 insulin is not FDA-approved for use in CSII and the ideal candidate should be intellectually able to deal with insulin pump therapy, this treatment was effective for our patient who required high insulin doses and failing other treatment regimen, achieving glycemic control and weight loss in six weeks. The only way this patient used this mode of insulin administration was on a single basal rate and fixed insulin bolus doses before each meal and with bedtime snack. All of these parameters were adjusted by 5 for the use of concentrated insulin in the pump device. HbA1c decreased from 10.5% to 8.5% with only six weeks of treatment and at one year decreased to even more 7.0%. Currently patient had been using CSII with U-500 for six years and patient HbA1c range is between 7.5-7.9% evaluated approximately every 3 months. Conclusion: The increase in the prevalence of obesity and diabetes has been an issue in treating patients who require high doses of insulin. The use of U-500 for CSII allows for better absorption of high insulin doses and improvement of glycemic control thus improving quality of life, weight loss, decreasing multiple daily injections and preventing diabetes complications. To our knowledge this is the first case report demonstrating long-term glycemic control with U-500 via CSII and on a fixed dose regimen on CSII without using carb counting or corrections to make this regimen easier for certain patients without the knowledge for complicated regimens.

Calcium is the fifth most abundant element in earth and human body. It has multiple functions within our system such bone mineralization, neuromuscular excitability regulation, hemostasis, membrane transport, release of hormones and neurotransmitters, among others. For duodenal absorption of calcium, we need vitamin D, reason for which supplementation of both components is important to maintain adequate calcium homeostasis. However, it is entirely beneficial or can be harmful? As we know everything in excess has its consequences, as we describe below. 72 y/o male is brought to the ED after relative find him lethargic, she reports noticing generalized weakness that has been progressing over weeks, prominent in upper extremities with associated increased in urinary frequency. Patient past medical history is relevant for CAD, hypothyroidism, dyslipidemia, and DMT2. On physical examination patient is found hypoactive, but arousable to verbal stimuli, without distress, focal neurologic deficit, thyromegaly nor lymphadenopathy. Presents with Ca+: 18.8mg/dL (n:8.0–10.5mg/dL), that could explain patient clinical presentation for which workup for hypercalcemia is done finding PTH suppress: 14.57pg/mL (n:15-65pg/mL). Patient now with non-PTH related hypercalcemia is further evaluated and found with negative UPEP and SPEP ruling out multiple myeloma and PTH-rp <2.0pmol/L (negative). While etiology of severe hypercalcemia is being study, patient complications of it are being managed such as AKI stage 3 as he presents with Cr: 3.85mg/dL, BUN: 62.5, CrCl:18ml/min and GFR: 15ml/min. Aggressive IV hydration and bisphosphonate therapy failed to decrease calcium and renal function continues worsens, for which hemodialysis is required for calcium clearance. Patient then found with vitamin D25-OH levels: 210.4ng/mL (n:30-100ng/mL), upon questioning he reports taking multivitamins and supplements equivalent for a daily ingestion of 50,700IU of Vitamin D3 and 334mg of calcium carbonate. Patient calcium levels normalize after dialysis but develops renal failure for which he has to be discharged on permanent hemodialysis. Although prevalence is unknown, hypercalcemia due to vitamin D intoxication is relatively uncommon in comparison to hyperparathyroidism and malignancy. An exact dose intake that leads to intoxication has not yet being stablished but supplementation besides dosage is also dependent on duration of therapy. This case has a lot to teach us, starting with detrimental effects of hypercalcemia, follow by the consequences of lack of counseling and close follow-up of patient over-the-counter supplementation. As physicians we should inquire more about OTC medications and supplements our patients are taking not only for intoxication concerns, but also for drugs interactions. Counseling must be the cornerstone of our practice to avoid life changing consequences as in this case.