Closed-Loop Insulin Delivery May Help Prevent Metabolic Complications During Bariatric Surgery in Patients with Type 1 Diabetes: A Case Report.

Introduction: Obesity in patients with type 1 diabetes (T1D) may worsen their prognosis. Bariatric surgery in these patients can be associated with complications such as diabetic ketoacidosis and severe hypoglycemic episodes. Closed-loop insulin delivery could be a solution to avoid them. Case Report: A 45-year-old woman with T1D and obesity (body mass index of 38.4 kg/m2) was included in our preoperative course of bariatric surgery. Three months before surgery, a closed-loop insulin delivery was instituted due to one prior severe hypoglycemia. Patient did not have immediate or late postoperative hypoglycemia despite consuming a weak amount of carbohydrate. Three months after surgery glycemic control was on target with 86% of time in range 70-180 mg/dL and no time below 70 mg/dL. Conclusion: This case report shows that the use of a closed-loop insulin delivery made it possible to perform bariatric surgery in complete safety for our patient.

Noninvasive Prenatal Diagnosis of a Paternally Inherited MEN1 Pathogenic Splicing Variant.

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease caused by mutations in the tumor suppressor gene MEN1. The uncertainty of pathogenicity of MEN1 variants complexifies the selection of the patients likely to benefit from specific care. OBJECTIVE: MEN1-mutated patients should be offered tailored tumor screening and genetic counseling. We present a patient with hyperparathyroidism for whom genetic analysis identified a variant of uncertain significance in the MEN1 gene (NM_130799.2): c.654G > T p.(Arg218=). Additional functional genetic tests were performed to classify the variant as pathogenic and allowed prenatal testing. DESIGN: Targeted next generation sequencing identified a synonymous variant in the MEN1 gene in a 26-year-old male with symptomatic primary hyperparathyroidism. In silico and in vitro genetic tests were performed to assess variant pathogenicity. RESULTS: Genetic testing of the proband's unaffected parents showed the variant occurred de novo. Transcript study showed a splicing defect leading to an in-frame deletion. The classification of the MEN1 variant as pathogenic confirmed the diagnosis of MEN1 and recommended an adapted medical care and follow-up. Pathogenic classification also allowed to propose a genetic counseling to the proband and his wife. Noninvasive prenatal diagnosis was performed with a personalized medicine-based protocol by detection of the paternally inherited variant in maternal plasmatic cell free DNA, using digital PCR. CONCLUSION: We showed that functional genetic analysis can help to assess the pathogenicity of a MEN1 variant with crucial consequences for medical care and genetic counseling decisions.

Combined 68Ga-DOTATOC and 18F-FDG PET Predicts a Double Component With Different Grade of a Pancreatic Neuroendocrine Tumor in a Patient With Multiple Endocrine Neoplasia Type 1.

Managing decisions of pancreatic neuroendocrine tumors (pNETs) can be challenging because of different clinical presentations and prognosis. A 31-year-old woman with multiple endocrine neoplasia type 1, including a suspicious pNET, was assessed with Ga-DOTATOC and F-FDG PET. A high Ga-DOTATOC uptake was visualized in the entire pNET, whereas a high F-FDG PET uptake was present only in the upper part of the tumor. After surgery, pathology confirmed the pNET with a double component: an upper grade 2 with a Ki67 of 11% with the high F-FDG PET uptake, and a lower grade 1 with a Ki67 of 2%. Combined Ga-DOTATOC/F-FDG PET predicts the grade in heterogeneous pNETs.

A Hungry Bone Syndrome Predicted by 18F-Fluorocholine PET/CT.

Predicting hungry bone syndrome (HBS) after surgical cure of primary hyperparathyroidism (PHPT) can be challenging. A 57-year-old man diagnosed with PHPT was assessed preoperatively by F-fluorocholine PET/CT. An intense and diffuse tracer uptake of the axial and peripheral skeleton was visualized, in addition to a pathologic uptake suggestive of hyperfunctioning parathyroid gland. After the removal of a parathyroid adenoma, a severe and prolonged HBS requiring high doses of calcium and active metabolites of vitamin D was observed. This observation suggests that intense and diffuse bone uptake on F-fluorocholine PET/CT could be a predictive factor for HBS in patients with PHPT.

Cabergoline Tapering Is Almost Always Successful in Patients With Macroprolactinomas.

CONTEXT: Cabergoline (CAB) is very effective in the treatment of macroprolactinomas, but there are few data on the CAB dose necessary to achieve and maintain normal prolactin (PRL) levels. DESIGN AND PATIENTS: We retrospectively studied 260 patients. CAB was introduced at a mean dose of 0.83 ± 0.52 mg/wk. When the PRL level had normalized, the patient's physician chose to either maintain the CAB dose (fixed-dose group) or to taper it (de-escalation group) until the minimal effective dose required to maintain a normal PRL level was established. RESULTS: PRL normalized in 157 patients (60.8%) during CAB treatment. CAB de-escalation was attempted in 84 (53.5%) of these 157 patients and was successful in 77 (91.7%) cases. The mean CAB dose was reduced from 1.52 ± 1.17 mg/wk to 0.56 ± 0.44 mg/wk at the last visit (P < 1 × 10-4). De-escalation was also possible in some "CAB-resistant" patients, namely those requiring ≥2 mg/wk to normalize PRL. CAB de-escalation had no negative long-term effect on tumor size. At the last visit, maximal diameter was 8.8 ± 8.8 mm in the de-escalation group and 13.4 ± 8.5 mm in the fixed-dose group (P < 0.01). CONCLUSION: In patients with macroprolactinomas, the CAB dosage required to maintain a normal PRL level long term is lower than the initial dosage necessary to normalize the PRL level. After PRL normalization, CAB tapering was almost always successful, even when very high initial doses were necessary. CAB tapering does not undermine tumor control and may attenuate the potential adverse effects of CAB, which appear to be dependent on the cumulative dose.

Polyendocrinopathy Resulting From Pembrolizumab in a Patient With a Malignant Melanoma.

INTRODUCTION: Checkpoint inhibitors have significantly improved the prognosis of patients with advanced melanoma. These cancer immunotherapy drugs have specific endocrine autoimmune toxicity. We describe a case of an adrenal insufficiency secondary to pembrolizumab, an anti-programmed cell death-1 monoclonal antibody. Moreover, this case of polyendocrinopathy resulting from a pembrolizumab as the adrenal insufficiency occurred after a thyroiditis. PARTICIPANT: A 55-year-old female was started on pembrolizumab immunotherapy for a metastatic choroidal melanoma. Five months after initiation, she suffered from thyrotoxicosis. A thyroiditis was diagnosed by iodine-123 thyroid scintigraphy and ultrasonography. Pembrolizumab therapy was maintained. Two weeks later, without any other treatment given, she patient developed hypothyroidism and levothyroxine substitution was started. Pembrolizumab proved to be ineffective and was stopped 9 months after initiation. One month following its discontinuation, the patient was hospitalized in the intensive care unit. Severe hyponatremia (115 mmol/L) associated with hyperkalemia (5.7 mmol/L) led to the early recognition and treatment of an acute adrenal insufficiency. Positive results for adrenal cortex and 21-hydroxylase antibodies were in favor of autoimmune toxicity. CONCLUSION: This case highlights the diversity of potential endocrine toxicity of checkpoint inhibitors. Because acute adrenal crisis may be associated with substantial morbidity and mortality, physicians must be aware of these rare adverse events to allow an early diagnosis.

Long-Term Control of Hypercortisolism by Vandetanib in a Case of Medullary Thyroid Carcinoma with a Somatic RET Mutation.

BACKGROUND: Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome (CS) have a poor prognosis, partially due to the difficulty in controlling hypercortisolism by adrenal blocking drugs. Recent reports (including the initial follow-up of this patient) have suggested that tyrosine kinase inhibitors (TKIs) may be a therapeutic option due to an anti-secretory action on ACTH. However, there is a lack of long-term follow-up studies. PATIENT FINDINGS: The case is reported of a 58-year-old man with MTC-related CS resistant to a combination of several anti-cortisolic drugs. Vandetanib, an oral multi-TKI that targets RET in particular, was initiated, and a rapid reversal of the hypercortisolism was observed without any change in tumor size. Vandetanib was briefly interrupted twice, once for 45 days because of side effects and a second time for 10 days to schedule surgical debulking. Each time, plasma cortisol and calcitonin levels increased after TKI withdrawal and were rapidly lowered by vandetanib reintroduction. As described in other cases of CS caused by MTC, a marked ACTH increase after desmopressin stimulation was observed before vandetanib therapy. In contrast, a blunted ACTH response to desmopressin was documented throughout the course of vandetanib treatment. This modulation of the tumoral ACTH production is a strong argument in favor of a TKI anti-secretory action. A left thyroid lobectomy and a modified neck dissection were performed one year after the initiation of vandetanib in order to reduce the tumor mass. An activating M918T RET (c.2753T>C) somatic mutation was identified in a lymph node metastasis. CONCLUSION: Three years and eight months after vandetanib initiation, there was no sign of recurrence of hypercortisolism. This case illustrates the long-term effectiveness of vandetanib in maintaining the control of hypercortisolism in MTC-related CS.

High levels of CRP in morbid obesity: the central role of adipose tissue and lessons for clinical practice before and after bariatric surgery.

BACKGROUND: Obesity, characterized by low-grade inflammation both in blood and white adipose tissue (WAT) is associated with increased C-reactive protein (CRP), a well-known acute phase protein. The aim of this study was to determine factors associated with high levels of CRP in obesity. METHODS: In 674 obese patients candidates to bariatric surgery (mean body mass index [BMI]=47.4±7.4 kg/m²), we examined the relationships between CRP and a series of bioclinical markers and histologic features of subcutaneous and omental WAT (scWAT) and liver. We also compared the same parameters after separating patients with "high" inflammation (HI, CRP≥20 mg/L, n=52) and with "low" inflammation (LI, CRP<20 mg/L, n=622). RESULTS: Mean CRP was 8.9±6.9 mg/L and positively correlated with fat mass (P<10(-4)). The HI group included predominantly women (92% versus 79%), of a younger age, with higher BMI (50.9±8.8 versus 47.1±7.2 kg/m2, P=.003), and fat mass (51.6 versus 48.8%, P<.001), higher prevalence of obstructive sleep apnea (OSA) (73% versus 57%, P=.02), and had increased number of HAM56+ immune cells in scWAT (20.8 versus 14.5%, P=.05). There was no difference in metabolic status, WAT fibrosis or liver histology findings between the groups. After 1 year of surgery-induced weight loss, 48 out of 52 patients with HI returned to CRP levels<20 mg/L. CONCLUSION: Our results suggest that WAT inflammation is a major contributor to increased CRP in obesity. In obese patients presenting high CRP levels with no obvious explanation, age, gender, BMI, fat mass proportion, OSA, and WAT inflammation should be taken into account to decide to perform further additional medical investigations.