Adverse Events Related to Tirzepatide.

Context: Tirzepatide is a dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) approved by the US Food and Drug Administration in May 2022 for patients with type 2 diabetes mellitus (T2DM). Objective: We aimed to determine the rates of individual adverse events (AEs) related to 3 studied doses of tirzepatide. Methods: We performed a systematic review with meta-analysis including 5 databases (PubMed, Embase, CINAHL, Scopus, and Web of Science) for all clinical trials reporting AEs related to tirzepatide. The safety data from individual studies were extracted and analyzed through meta-regression to assess rates of individual AEs. Study quality assessment was performed using the National Heart, Lung, and Blood Institute Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: Ten trials (6836 participants) were included. Gastrointestinal (GI) AEs were the most commonly reported AEs and were dose dependent 39% (95% CI, 35%-43%), 46% (95% CI, 42%-49%), and 49% (95% CI, 38%-60%) for the 5, 10, and 15 mg dose, respectively. Among all GI AEs, nausea and diarrhea were most frequent at any dose of tirzepatide. Drug discontinuation due to AEs was highest with the 15 mg dose of tirzepatide (10%). Incidence of mild hypoglycemia (blood glucose < 70 mg/dL) was highest with tirzepatide 10 mg dose 22.6% (9.2%-39.8%). Rates of fatal AEs, severe hypoglycemia, acute pancreatitis, cholelithiasis, and cholecystitis were extremely low (≤ 1%) across all doses of tirzepatide. Conclusion: Tirzepatide is associated with a dose-dependent increase in incidence of GI AEs and AEs leading to drug discontinuation. Severe hypoglycemia, fatal AEs, acute pancreatitis, cholelithiasis, and cholecystitis are rare with this medication.

A Case of Undiagnosed Functional Gonadotroph Adenoma Leading to Ovarian Hyperstimulation Syndrome.

A functional gonadotroph adenoma is a very rare endocrinopathy, and only a few cases have been reported in the literature. We present a case of a woman in her early 50s with a past medical history of recurrent ovarian cysts who developed bilateral hemianopsia and was referred to the endocrinology clinic after a magnetic resonance imaging (MRI) identified a pituitary mass. Anterior pituitary hormone workup confirmed hypersecretion of follicle-stimulating hormone (FSH), which suggested ovarian hyperstimulation syndrome (OHSS) as the etiology of recurrent ovarian cysts. The patient underwent transsphenoidal resection of the pituitary tumor with improvement in visual symptoms. Our case illustrates that functional gonadotroph adenoma can be a potential cause of OHSS apart from the setting of assisted reproductive technology and hence warranting a meticulous endocrine evaluation to rule out this rare disease.

Case report: SARS-CoV-2 infection as a trigger for diabetic ketoacidosis and newly detected pancreatic autoantibodies.

A 39-year-old-woman with a past medical history of type 2 diabetes mellitus (T2DM) on oral hypoglycemic agents presented to the emergency room with nausea, vomiting, shortness of breath, and altered mental status. Seven days prior to presentation, she was diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Laboratory workup on presentation confirmed the diagnosis of diabetic ketoacidosis (DKA) (blood glucose 523 mg/dl, beta-hydroxybutyrate 8.91 mmol/l, pH 6.9, bicarbonate 11 mEq/l, anion gap 25 mEq/l, and HbA1c 10.8%). She was managed for DKA with hydration and insulin drip and discharged home. However, to our surprise, at the 2-week follow-up visit, she was found to have positive antibodies for zinc transporter 8 (ZnT8) (samples were collected on day of presentation). The rest of her antibodies associated with T1DM were negative. She was therefore started on a basal-bolus regimen and managed as type 1 diabetes mellitus (T1DM). Our case illustrates that there is an increased risk of T1DM following infection with SARS-CoV-2.

Sodium-glucose cotransporter 2 inhibitor-associated severe epididymo-orchitis.

A man in his late 50s, with uncontrolled type 2 diabetes mellitus (T2DM) and morbid obesity, presented to the hospital with complicated epididymo-orchitis. The onset of symptoms (scrotal pain, erythema and swelling) occurred after the use of empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, for 2 months. His baseline antidiabetic medications were insulin, glipizide and metformin. Initially, he had failed treatment of epididymo-orchitis with oral levofloxacin for 3 weeks, followed by 2 weeks of doxycycline therapy. At the presentation to the hospital, an ultrasound of the scrotum revealed scrotal and right testicular abscess. The patient underwent right inguinal orchiectomy. Postoperatively, pus culture was positive for Enterococcus faecalis and Candida glabrata, and hence, he was treated with oral antibiotics including high-dose antifungal medications. Adequate wound care and regular follow-up demonstrated resolution of infection. This case highlights the risk of severe urogenital infection associated with the use of SGLT2 inhibitors in the setting of uncontrolled T2DM.

Late onset of pituitary apoplexy following gonadotropin-releasing hormone agonist for prostate cancer treatment.

Pituitary apoplexy (PA) is a clinical condition characterised by a sudden increase in pituitary gland volume secondary to ischaemia and/or necrosis. Most cases occur in non-functioning pituitary adenoma but can also occur in functioning adenoma. Certain predisposing factors can result in PA and the use of gonadotropin-releasing hormone (GnRH) agonists for prostate cancer (PCa) is one such condition. Once diagnosed, both surgical and conservative management has been used for the treatment of PA. We present a case of a man in his late 50s who developed PA following treatment of PCa with leuprolide. His symptoms developed insidiously and he presented 6 months after symptom onset. Anterior pituitary hormone workup along with pituitary MRI confirmed the diagnosis of PA and patient was subsequently treated with adequate replacement of pituitary hormone with significant improvement in his symptoms. It is very important to keep a high index of suspicion for PA, especially among elderly patients receiving GnRH agonist treatment for PCa.

Dermatologic Manifestations of Endocrine Disorders.

Endocrine disorders are known to involve all organ systems of the body, including the skin. The cutaneous manifestations of endocrine disorders can range from common findings such as acanthosis nigricans, pretibial myxedema, acne, hirsutism, hyper or hypopigmentation to rare cutaneous findings such as miliaria rubra, calciphylaxis, lentigines, and calcinosis cutis. These cutaneous symptoms can sometimes be the presenting symptoms or can even be pathognomonic of the underlying endocrine condition. In some cases, the cutaneous symptoms from an underlying endocrine abnormality may be the most prominent. These symptoms can significantly affect the quality of life of individuals. Often, individuals may seek health care from a dermatologist or primary care physician for isolated skin symptoms. Therefore, it is imperative for physicians to recognize the skin symptoms as the manifestation of the endocrine disorder for prompt diagnosis and treatment of the underlying endocrine disorder.

Pituitary apoplexy induced by gonadotropin-releasing hormone (GnRH) agonist administration for treatment of prostate cancer: a systematic review.

OBJECTIVE: We aimed to review of literature on the clinical presentation, management and outcomes of pituitary apoplexy following gonadotrophic release hormone (GnRH) agonist administration for the treatment of prostate cancer. METHODS: We used PRISMA guidelines for our systematic review and included all English language original articles on pituitary apoplexy following GnRH agonist administration among prostate cancer patients from Jan 1, 1995 to Dec 31, 2020. Data on patient demographics, prostate cancer type, Gleason score at diagnosis, history of pituitary adenoma, clinical presentation, GnRH agonist, interval to pituitary apoplexy, laboratory evaluation at admission, radiologic findings, treatment of pituitary apoplexy, time to surgery if performed, pathology findings, and clinical/hormonal outcomes were collected and analyzed. RESULTS: Twenty-one patients with pituitary apoplexy met our inclusion criteria. The mean age of patients was 70 (60-83) years. Leuprolide was the most common used GnRH agonist, used in 61.9% of patients. Median duration to symptom onset was 5 h (few minutes to 6 months). Headache was reported by all patients followed by ophthalmoplegia (85.7%) and nausea/vomiting (71.4%). Three patients had blindness at presentation. Only 8 cases reported complete anterior pituitary hormone evaluation on presentation and the most common endocrine abnormality was FSH elevation. Tumor size was described only in 15 cases and the mean tumor size was 26.26 mm (18-48 mm). Suprasellar extension was the most common imaging finding seen in 7 patients. 71.4% of patients underwent pituitary surgery, while 23.8% were managed conservatively. Interval between symptoms onset to pituitary surgery was 7 days (1-90 days). Gonadotroph adenoma was most common histopathologic finding. Clinical resolution was comparable, while endocrine outcomes were variable among patients with conservative vs surgical management. CONCLUSION: Although the use of GnRH agonists is relatively safe, it can rarely lead to pituitary apoplexy especially in patients with pre-existing pituitary adenoma. Physicians should be aware of this complication as it can be life threatening. A multidisciplinary team approach is recommended in treating individuals with pituitary apoplexy.

Isolated Adrenocorticotropic Hormone Deficiency Secondary to Chronic Opiate Use.

Although opiate use can result in various endocrine disorders, isolated adrenocorticotropic hormone (ACTH) deficiency resulting in secondary adrenal insufficiency remains uncommon. We present a case of a 54-year-old woman with a history of chronic opiate use who presented with a four-month history of worsening fatigue and syncopal episodes. Laboratory workup revealed a low ACTH with low baseline cortisol and normal levels of rest of the anterior pituitary hormones. The imaging study did not reveal any pituitary abnormality. The patient was diagnosed with opiate-induced isolated ACTH deficiency. Her symptoms improved after treatment with hydrocortisone. This case would further improve clinician's awareness towards opiate-induced endocrinopathies, including isolated ACTH deficiency, which can present with nonspecific signs and symptoms, creating a diagnostic challenge.

The Use of 99mTc-Methoxy-isobutyl-isonitrile (sestaMIBI) Uptake on Scintigraphy (99m-STS) in Amiodarone-Induced Thyrotoxicosis: Case Series and Review of the Literature.

Amiodarone is a class III antiarrhythmic drug, used by cardiologists to treat arrhythmia including atrial fibrillation (A fib) and ventricular fibrillation. However, amiodarone is associated with endocrine dysfunction including both hypo- and hyperthyroidism. In the literature, two types of amiodarone-induced thyrotoxicosis (AIT) were described: AIT-1 and AIT-2. Mixed AIT also called AIT type 3 (AIT-3) has been described in the literature when the cases do not have a typical presentation. In order to differentiate different types of AIT, various clinical, biochemical, and radiological tools have been proposed. The use of 99mTc-methoxy-isobutyl-isonitrile (sestaMIBI) uptake on scintigraphy (99m-STS) has been suggested in the literature in only few studies (no large retrospective or prospective studies have been established in the United States). We present a case series describing 5 patients presenting to the University of Arizona with AIT where we used 99m-STS to assess in diagnosis and treatment of different types of AIT followed by a review of the literature.

Unmasked Testicular Seminoma During Use of Hormonal Transgender Woman Therapy: A Hidden hCG-Secreting Tumor.

Management of gender-affirming hormone therapy (HT) in transgender women includes surveillance of testosterone (T) levels. Failure of T to suppress, despite adherence to therapy, warrants additional investigations for unexpected sources of T or factors stimulating T secretion. Possible causes include T or gonadotropin production by an occult neoplasm. Testicular cancer is the most common malignancy affecting biological men aged between 15 and 35 years. Patients may be asymptomatic until tumor burden is high and/or metastatic. Hormone-producing tumors have rarely been reported in treated transgender women. Routine screening tests are recommended in a gender-incongruent person as per the 2017 Endocrine Society guidelines with measurement of T levels every 3 months initially to reach a goal of less than 50 ng/dL. Expectations should be discussed in detail with the transgender person since anticipated physical changes may not be notable for 6 to 18 months. We herein describe a case of a transgender woman who underwent standard HT including gonadotropin suppression with a gonadotropin-releasing hormone agonist, whose total T level failed to suppress. Testing revealed an elevated serum level of the beta subunit of human chorionic gonadotropin (ß-hCG), diagnostic of an hCG-secreting testicular seminoma, as the underlying cause of unexpected T production. This case illustrates how easily a testicular cancer can remain unnoticed because it can be asymptomatic and the necessity to be alert to, and act on, anomalous laboratory results during treatment of a transgender person.

Tyrosine Kinase Inhibitors' Newly Reported Endocrine Side Effect: Pazopanib-Induced Primary Adrenal Insufficiency in a Patient With Metastatic Renal Cell Cancer.

Tyrosine kinase inhibitors (TKIs) have been used in the treatment of multiple types of cancer. Pazopanib is one of the TKIs and is considered a first-line treatment for adult patients with metastatic renal cell carcinoma. Many endocrine-related adverse effects have been noted with the use of TKIs including hypothyroidism, vitamin D deficiency, altered bone density, secondary hyperparathyroidism, abnormal glucose metabolism, gynecomastia, and hypogonadism. Subclinical glucocorticoid deficiency and adrenal insufficiency have been reported with the use of TKIs in only a few cases so far; thus, its true prevalence and clinical significance have yet to be fully elucidated. The mechanism is still not fully understood; however, adrenal toxicity with hemorrhage and/or necrosis of the adrenal glands has been observed in studies. In this article, we describe the first reported case of pazopanib inducing primary adrenal insufficiency in a patient with metastatic renal cell carcinoma diagnosed after the exclusion of all other causes of primary adrenal insufficiency.

The status of diabetes and its complications in Latin-American population: A review article.

The Latino population consists of distinct cultural groups, with differences in dietary habits and lifestyle that can affect the risk for type 2 diabetes. The best terminology today is Latino/Hispanic, and it should only be used as ethnicity. Latin-America has different races such as Caucasians, Native Americans, Blacks and Asians, and many mixtures of all. The leading cause of death in Latin-America is Cardiovascular diseases and the most important risk factor is diabetes mellitus (DM). According to the latest estimates from the Global Burden of Disease, the burden of DM was greater than expected in Latin America and the Caribbean region. Extensive data illustrates that lower cardiovascular disease risk in Latino group is a paradox. Instead, it is evident that the cardiovascular disease is the leading cause of mortality in Latinos.

Adrenocortical carcinoma: a literature review.

Adrenocortical carcinoma (ACC) is reported to be present in 3-10% of the population with most tumors presenting as benign tumors. Most cases of ACC are a sporadic accumulation of mutations over time. However, studies show a predisposition to various genetic mutations may contribute. Research over the last couple of decades has elucidated causes of ACC to be driven by several molecular changes that include inactivation of tumor suppressor genes and activation of a myriad of different oncogenes, DNA mutations, and epigenetic changes. The widely adopted staging of ACC is by European Network of Study of Adrenal Tumors (ENSAT) due to its correlations with clinical outcomes. At the time of presentation, a detailed history taking with attention to the history of symptoms of hormonal excess and family history of possible hereditary influence is the first step of evaluation. It is followed by a thorough physical examination for evaluation of ACC. Management of ACC poses a unique challenge as it involves oncologic and endocrine issues. Except for one trial, treatment guidelines are based on retrospective studies and non-randomized trials, and therefore the level of evidence is grade II to grade IV. Personalized therapy including identifying the actionable target in each patient is the future of ACC management. The knowledge base of ACC is evolving based on the basic science and clinical trials conducted by worldwide groups such as COMITE of France, ENSAT of Europe, TCGA project and American Australian Asian Adrenal Alliance (A5). Future studies should aim at clear molecular and clinical standardization. Recommended therapeutic strategies should be prospectively recorded.

An Unusual Benign Cause of an Alarming Finding on Chest-X ray: A Case Report of Widened Mediastinum due to Rare Congenital Abnormality (Azygos Vein Continuation of Inferior Vena Cava).

Acute widened mediastinum is an alarming finding. It has many possible differential diagnoses; aortic dissection (AD) is considered one that carries catastrophic outcomes. AD is relatively uncommon; it requires early and accurate diagnosis and treatment for better patient survival. However, acute mediastinal widening also can be present in more benign conditions. We report a case of a 50-year-old African American female with postoperative shortness of breath; initial imaging studies revealed an acute widened mediastinum, but on further management with diuresis and follow-up imaging, she was diagnosed with azygous vein continuation of the Inferior vena cava (IVC). This is considered as a rare benign cause of wide mediastinum. Clinicians must be aware of the presence of such a benign cause when dealing with acute wide mediastinum.

Sudden-onset Hypoglycemia Following Fluid Replacement in a Patient with Dapagliflozin-induced Diabetic Ketoacidosis Without Prior Insulin Use: Case Report.

Euglycemic diabetic ketoacidosis (DKA) is a known complication of sodium-glucose co-transporter 2 (SGLT-2) inhibitors that have been reported in the literature. The prevalence of this side effect is growing and the exact mechanism of action on why this happens is unknown. Hypoglycemia events are very rare in diabetic patients using SGLT-2 inhibitors and/or metformin when they have normal kidney function. We report a novel complication of hypoglycemia that occurred during the course of treatment of SGLT2 inhibitor-induced DKA in a patient with type 2 diabetes mellitus (T2DM) on the dapagliflozin-metformin combination.

Simple Reason for Hypoglycemia: ACE Inhibitor-induced Severe Recurrent Hypoglycemia in a Nondiabetic Patient.

Angiotensin-converting enzyme (ACE) inhibitors are among the most common medications used to treat patients with concomitant diabetes and hypertension. They are considered the first line of treatment for hypertension in this population. Several case studies have reported that ACE inhibitors can induce hypoglycemia in patients with diabetes. To our knowledge, however, ACE inhibitors have not been found to induce hypoglycemia in patients without diabetes. This report describes a patient without diabetes experiencing recurrent severe hypoglycemia induced by the ACE inhibitor lisinopril.

Early Presentation of a Rare Complication of Sodium-Glucose Cotransporter-2 Inhibitors 10 Days After Initiation: Case Report and Literature Review.

Fournier's gangrene is an extremely rare infection that can occur in immunocompromised patients, especially those with diabetes. Given the severity of this infection and the new associated link to sodium-glucose cotransporter-2 inhibitors, the US FDA recently issued a warning in August 2018. Few cases of Fournier's gangrene have been reported in the literature in diabetic patients taking these oral medications. We report a case of Fournier's gangrene presenting 10 days after a patient with type 2 diabetes started empagliflozin therapy.

Right Atrial Fibroelastoma Presenting as Typical Atrial Flutter: Rare Disease in Unusual Location.

Typical atrial flutter as initial presentation of papillary fibroelastoma involving the cavotricuspid isthmus is not described before in literature. To our knowledge only 14 cases have been reported in literature involving the right atrium. Very unusual location is at the junction between inferior vena cava (IVC) and right atria as only 1 case has been reported.

Intracranial Hemorrhage Complicating Herpes Simplex Encephalitis on Antiviral Therapy: A Case Report and Review of the Literature.

Herpes simplex virus (HSV) encephalitis is the most common cause of nonendemic sporadic encephalitis in the USA. Decreased mortality with early treatment with acyclovir has been documented. Although common complications include cortical petechial hemorrhages, frank intracerebral hematomas are considered very rare. Only few cases have been reported in the literature. We report a case of HSV encephalitis complicated by intracerebral hemorrhage 12 days after initiation of acyclovir therapy.