A Case of Metastatic Choriocarcinoma-Related Paraneoplastic Thyroid Storm.

Thyroid storm due to gestational trophoblastic disease (GTD) with metastatic choriocarcinoma is a rare but potentially life-threatening endocrine emergency. We report on a woman with molar pregnancy and metastatic choriocarcinoma who presented with thyroid storm (Burch-Wartofsky point scale of 45) a few weeks after the evacuation of GTD. She was initially managed with intravenous hydrocortisone, oral propylthiouracil (PTU), and esmolol infusion. After stabilization in the intensive care unit, 10 cycles of chemotherapy with etoposide, methotrexate, leucovorin, dactinomycin, and cyclophosphamide (EMA-CO) were initiated for stage 4 choriocarcinoma with brain and lung metastases. She underwent a hysterectomy soon after completing chemotherapy and received an additional 3 cycles of chemotherapy after the hysterectomy. As human chorionic gonadotropin (hCG) levels normalized, thyroid function reverted to normal as well. At the last follow-up, the patient was asymptomatic, euthyroid (without antithyroid medication), had a normal hCG titer of 1.7 mIU/mL (normal nonpregnant reference is < 5 mIU/mL), and the lung and brain lesions had resolved entirely. Management of thyroid storm in the presence of untreated metastatic choriocarcinoma requires a high index of suspicion and a multidisciplinary team approach to prevent complications and improve survival.

In T2DM uncontrolled with noninsulin glucose-lowering agents, weekly icodec reduced HbA1c vs. daily degludec at 26 wk.

SOURCE CITATION: Lingvay I, Asong M, Desouza C, et al. Once-weekly insulin icodec vs once-daily insulin degludec in adults with insulin-naive type 2 diabetes: the ONWARDS 3 randomized clinical trial. JAMA. 2023;330:228-237. 37354562.

In T2DM uncontrolled with noninsulin glucose-lowering agents, weekly icodec reduced HbA1c vs. daily glargine at 52 wk.

SOURCE CITATION: Rosenstock J, Bain SC, Gowda A, et al; ONWARDS 1 Trial Investigators. Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin. N Engl J Med. 2023;389:297-308. 37356066.

In uncontrolled T2DM treated with a basal-bolus insulin regimen, weekly icodec was noninferior to daily glargine for HbA1c at 26 wk.

SOURCE CITATION: Mathieu C, Ásbjörnsdóttir B, Bajaj HS, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial. Lancet. 2023;401:1929-1940. 37156252.

In pituitary adenoma surgery, no vs. perioperative hydrocortisone was noninferior for new-onset adrenal insufficiency.

SOURCE CITATION: Guo X, Zhang D, Pang H, et al. Safety of withholding perioperative hydrocortisone for patients with pituitary adenomas with an intact hypothalamus-pituitary-adrenal axis: a randomized clinical trial. JAMA Netw Open. 2022;5:e2242221. 36383383.

Clinical Considerations for Insulin Therapy in Older Adults with Type 1 Diabetes.

Type 1 diabetes represents an autoimmune condition with a strong inherited background, and its incidence is increasing worldwide. About 25% of such cases are diagnosed in adulthood, some even as late as the ninth decade of life. The number of older adults with type 1 diabetes is increasing due to improvements in care and decreased mortality rate. However, there is a lack of clinical trials in people older than 70 years of age with type 1 diabetes complicated with comorbidities, frailty, and dependency. The management of type 1 diabetes and the goals of therapy should be individualized based on the patient's health status and life expectancy. In healthier older adults, insulin treatment regimens (multiple daily insulin injections or insulin pump therapy) that approximate the normal physiology of insulin secretion should be used to achieve lower glycemic goals, while reducing the risk of hypoglycemia with frequent glucose monitoring (preferably using continuous glucose monitoring systems). For frail individuals with poor health, simpler insulin regimens and less stringent glycemic targets would be more appropriate. Poor cognition, vision and hearing, impaired mobility, depression, and chronic pain can interfere with complex insulin regimens. In these individuals, the principal goals of therapy are to reduce the acute effects of hyperglycemia, minimize hypoglycemia risk, and optimize quality of life. The newer insulin preparations and technological advances in insulin delivery and blood glucose monitoring have enhanced the management of type 1 diabetes in all age groups.

Management of Hyperglycemia in Older Adults with Type 2 Diabetes.

The increasing incidence of type 2 diabetes in the general population as well as enhanced life expectancy has resulted in a rapid rise in the prevalence of diabetes in the older population. Diabetes causes significant morbidity and impairs quality of life. Managing diabetes in older adults is a daunting task due to unique health and psychosocial challenges. Medical management is complicated by polypharmacy, cognitive impairment, urinary incontinence, injurious falls, and persistent pain. Health care providers now have several traditional and contemporary pharmacologic agents to manage diabetes. Avoidance of hypoglycemia is critical; however, evidence-based guidelines are lacking due to the paucity of clinical trials in older adults. For many in this population, maintaining independence is more important than adherence to published guidelines to prevent diabetes complications. The goal of diabetes care in older adults is to enhance the quality of life without subjecting these patients to intrusive and complicated interventions. Recent technological advancements such as continuous glucose monitoring systems can have crucial supplementary benefits in the geriatric population.

In type 2 diabetes, tirzepatide reduced HbA1c vs. semaglutide.

SOURCE CITATION: Frias JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503-15. 34170647.

Clavicular Metastasis as an Initial Presentation of Papillary Thyroid Cancer.

OBJECTIVE: We present the case of a 44-year-old man with a large neck mass to highlight the unique presentation of papillary thyroid carcinoma (PTC) metastatic to the clavicle. METHODS: We reviewed the medical record for a detailed history and physical examination findings. Our radiology colleagues examined the diagnostic imaging studies performed. The pathology team reviewed the neck mass biopsy and the confirmatory surgical pathology after total resection of the mass. RESULTS: A 44-year-old man presented with an enlarging neck mass. Initial X-rays revealed a large soft tissue density mass that extended to the midline of the right clavicle. A neck ultrasound established a 5.4 × 3.6 cm mass with increased vascularity and calcification extending from the thyroid. A CT scan noted the extension of the mass into the adjacent sternoclavicular junction with osteolysis of the middle third of the clavicle and the superior aspect of the sternal body. Fine-needle aspiration revealed a thyroid neoplasm with follicular features and positive immunostaining consistent with thyroid carcinoma. The patient underwent a composite resection of the tumor, including a segmental osteotomy of approximately two-thirds of the medial clavicle. The pathology report confirmed PTC with extrathyroidal extension and clavicle involvement (staged pT4a pN0), with further genomic findings showing positive KRAS mutation. CONCLUSION: Clavicular metastasis from differentiated thyroid cancer is rare. While the prognosis is generally favorable, various factors, including age greater than 45 years, poor differentiation, follicular thyroid carcinoma, Hurthle cell variant, and extrapulmonary metastasis, have typically been associated with poorer cancer-specific survival.

In type 2 diabetes, some glucose-lowering drugs reduce HbA1c more than others; drugs do not differ for mortality.

SOURCE CITATION: Tsapas A, Avgerinos I, Karagiannis T, et al. Comparative effectiveness of glucose-lowering drugs for type 2 diabetes: a systematic review and network meta-analysis. Ann Intern Med. 2020;173:278-86. 32598218.

Symptomatic Pituitary Metastasis as Initial Manifestation of Renal Cell Carcinoma: Case Report and Review of Literature.

Metastasis to the pituitary gland is extremely rare (∼2% of sellar masses). Clinical, biochemical, and radiologic characteristics of pituitary metastasis are poorly defined and can be difficult to diagnose before surgery. We present an unusual case with pituitary metastasis as the first manifestation of renal cell carcinoma (RCC). A 70-year-old male presented with acute onset of weakness, dizziness, diplopia, and progressively worsening headache. The initial CT head revealed a heterogeneous sellar mass measuring 2.8 × 1.9 × 1.7 cm. A follow-up MRI showed the sellar mass invading the right cavernous sinus. The presumptive diagnosis was a pituitary macroadenoma. Physical examination revealed bilateral 6th cranial nerve palsy and episodes of intermittent binocular horizontal diplopia. Hormonal testing noted possible secondary adrenal insufficiency (AM serum cortisol: 3.3 mcg/dL, ACTH: 8 pg/mL), secondary hypothyroidism (TSH: <0.01 mIU/L, FT4: 0.7 ng/dL), secondary hypogonadism (testosterone: 47 ng/dL, LH: 1.3 mIU/mL, and FSH: 2.3 mIU/mL), and elevated serum prolactin (prolactin: 56.8 ng/ml, normal: 4.0-15.2 ng/ml). IGF-1 level was normal at 110 ng/mL (47-192 ng/mL). The patient was discharged on levothyroxine and hydrocortisone therapy with plans for close surveillance. However, his condition worsened over the next three months, and he was subsequently readmitted with nausea, vomiting, and hypernatremia secondary to diabetes insipidus. Repeat MRI pituitary showed an interval increase in the size of the sellar mass with suprasellar extension and a new mass effect on the optic chiasm. The sellar mass was urgently resected via a trans-sphenoidal approach. The tumor was negative for neuroendocrine markers and pituitary hormone panel, ruling out the diagnosis of pituitary adenoma and triggered workup for metastatic renal cell carcinoma, clear cell type. The diagnosis of renal cell carcinoma was confirmed by the diffuse and strong staining for renal cell carcinoma markers (Pax-8, RCC-1, and CD10). A follow-up CT scan noted large right renal mass measuring 11 × 10 × 11 cm. The patient underwent a cytoreductive robotic right radical nephrectomy for WHO/ISUP histologic grade II clear cell RCC, stage pT2b pNX pM1. He subsequently received fractionated stereotactic radiotherapy to the pituitary gland. He is presently stable with no radiological evidence of progression or new intracranial disease on subsequent imaging. Pituitary metastasis most commonly occurs from breast, lung, or gastrointestinal tumors but also rarely from renal cell carcinoma. Biochemical findings such as panhypopituitarism, acute clinical signs such as headache, visual symptoms, and diabetes insipidus and interval increase in sellar mass in a short time interval should raise suspicion for sellar metastasis.

Treatment of hyperprolactinemia: a systematic review and meta-analysis.

BACKGROUND: Hyperprolactinemia is a common endocrine disorder that can be associated with significant morbidity. We conducted a systematic review and meta-analyses of outcomes of hyperprolactinemic patients, including microadenomas and macroadenomas, to provide evidence-based recommendations for practitioners. Through this review, we aimed to compare efficacy and adverse effects of medications, surgery and radiotherapy in the treatment of hyperprolactinemia. METHODS: We searched electronic databases, reviewed bibliographies of included articles, and contacted experts in the field. Eligible studies provided longitudinal follow-up of patients with hyperprolactinemia and evaluated outcomes of interest. We collected descriptive, quality and outcome data (tumor growth, visual field defects, infertility, sexual dysfunction, amenorrhea/oligomenorrhea and prolactin levels). RESULTS: After review, 8 randomized and 178 nonrandomized studies (over 3,000 patients) met inclusion criteria. Compared to no treatment, dopamine agonists significantly reduced prolactin level (weighted mean difference, -45; 95% confidence interval, -77 to -11) and the likelihood of persistent hyperprolactinemia (relative risk, 0.90; 95% confidence interval, 0.81 to 0.99). Cabergoline was more effective than bromocriptine in reducing persistent hyperprolactinemia, amenorrhea/oligomenorrhea, and galactorrhea. A large body of noncomparative literature showed dopamine agonists improved other patient-important outcomes. Low-to-moderate quality evidence supports improved outcomes with surgery and radiotherapy compared to no treatment in patients who were resistant to or intolerant of dopamine agonists. CONCLUSION: Our results provide evidence to support the use of dopamine agonists in reducing prolactin levels and persistent hyperprolactinemia, with cabergoline proving more efficacious than bromocriptine. Radiotherapy and surgery are useful in patients with resistance or intolerance to dopamine agonists.

Tumor-induced osteomalacia caused by primary fibroblast growth factor 23 secreting neoplasm in axial skeleton: a case report.

We report the case of a 66-year-old woman with tumor-induced osteomalacia (TIO) caused by fibroblast growth factor 23 (FGF-23) secreting mesenchymal tumor localized in a lumbar vertebra and review other cases localized to the axial skeleton. She presented with nontraumatic low back pain and spontaneous bilateral femur fractures. Laboratory testing was remarkable for low serum phosphorus, phosphaturia, and significantly elevated serum FGF-23 level. Magnetic resonance imaging (MRI) of the lumbar spine showed a focal lesion in the L-4 vertebra which was hypermetabolic on positron emission tomography (PET) scan. A computed tomography (CT) guided needle biopsy showed a low grade spindle cell neoplasm with positive FGF-23 mRNA expression by reverse transcriptase polymerase chain reaction (RT-PCR), confirming the diagnosis of a phosphaturic mesenchymal tumor mixed connective tissue variant (PMTMCT). The patient elected to have surgery involving anterior resection of L-4 vertebra with subsequent normalization of serum phosphorus. Including the present case, we identified 12 cases of neoplasms localized to spine causing TIO. To our knowledge, this paper represents the first documented case of lumbar vertebra PMT causing TIO. TIO is a rare metabolic bone disorder that carries a favorable prognosis. When a lesion is identifiable, surgical intervention is typically curative.

Efficacy of continuous glucose monitoring in improving glycemic control and reducing hypoglycemia: a systematic review and meta-analysis of randomized trials.

OBJECTIVE: We conducted a systematic review and meta-analysis to assess the efficacy of continuous glucose monitoring (CGM) in improving glycemic control and reducing hypoglycemia compared to self-monitored blood glucose (SMBG). METHODS: We searched MEDLINE, EMBASE, Cochrane Central, Web of Science, and Scopus for randomized trials of adults and children with type 1 or type 2 diabetes mellitus (T1DM or T2DM). Pairs of reviewers independently selected studies, assessed methodological quality, and extracted data. Meta-analytic estimates of treatment effects were generated using a random-effects model. RESULTS: Nineteen trials were eligible and provided data for meta-analysis. Overall, CGM was associated with a significant reduction in mean hemoglobin A1c [HbA1c; weighted mean difference (WMD) of -0.27% (95% confidence interval [CI] -0.44 to -0.10)]. This was true for adults with T1DM as well as T2DM [WMD -0.50% (95% CI -0.69 to -0.30) and -0.70 (95% CI, -1.14 to -0.27), respectively]. No significant effect was noted in children and adolescents. There was no significant difference in HbA1c reduction between studies of real-time versus non-realtime devices (WMD -0.22%, 95% CI, -0.59 to 0.15 versus -0.30%, 95% CI, -0.49 to -0.10; p for interaction 0.71). The quality of evidence was moderate due to imprecision, suggesting increased risk for bias. Data for the incidence of severe or nocturnal hypoglycemia were sparse and imprecise. In studies that reported patient satisfaction, users felt confident about the device and gave positive reviews. CONCLUSION: Continuous glucose monitoring seems to help improve glycemic control in adults with T1DM and T2DM. The effect on hypoglycemia incidence is imprecise and unclear. Larger trials with longer follow-up are needed to assess the efficacy of CGM in reducing patient-important complications without significantly increasing the burden of care for patients with diabetes.