Persistent post-bariatric-surgery hypoglycemia: A long-term follow-up reassessment.

BACKGROUND AND AIM: Post-bariatric-surgery hypoglycemia (PBH) is a serious complication of bariatric surgery (BS). In our previous study about three quarters of the patients developed PBH. However long-term follow-up data is lacking to determine whether this condition improves with time. The aim of the current study was to re-assess post-BS patients who participated in our previous study and determine whether there are changes in the frequency and/or severity of hypoglycemic events. METHODS AND RESULTS: Twenty-four post-BS, post Roux-en-Y gastric-bypass (RYGB = 10), post omega-loop gastric-bypass (OLGB = 9) and post sleeve-gastrectomy (SG = 5) individuals were reevaluated in a follow-up study 34.4 ± 4 months after their previous assessment and 67 ± 17 months since surgery. The evaluation included: a dietitian assessment, a questionnaire, meal-tolerance test (MTT) and a one-week masked continuous glucose monitoring (CGM). Hypoglycemia and severe hypoglycemia were defined by glucose levels ≤54 mg/dl and ≤40 mg/dl, respectively. Thirteen patients reported questionnaire meal-related complaints, mainly non-specific. During MTT, hypoglycemia occurred in 75% of the patients, and severe hypoglycemia in a third, but none was associated with specific complaints. During CGM, 66% of patients developed hypoglycemia and 37% had severe hypoglycemia. We did not observe significant improvements in hypoglycemic events compared to the previous assessment. Despite the high frequency of hypoglycemia, it did not necessitate hospitalizations or lead to death. CONCLUSIONS: PBH did not resolve within long-term follow-up. Intriguingly, most patient were unaware of these events which can lead to underestimation by the medical staff. Further studies are needed to determine possible long term sequela of repeated hypoglycemia.

Prenatal Breastfeeding Counseling Intervention in Women with Pre-Gestational Diabetes Mellitus-A Randomized Controlled Trial.

BACKGROUND: Data on breastfeeding rates and targeted interventions in women with pre-gestational diabetes mellitus are inconclusive. The aim of the study was to evaluate breastfeeding rates up to one year postpartum and whether targeted counseling towards the end of pregnancy can impact breastfeeding rates and duration. An additional goal was to evaluate whether counseling affected women's perceptions regarding breastfeeding. METHODS: Women with pre-gestational diabetes mellitus were cluster-randomized between 32 and 36 weeks of gestation, either to face-to-face instruction with a certified lactation consultant or to receive written information on breastfeeding. Thirty-eight women without diabetes served as controls and were given written information on breastfeeding. All women filled out a questionnaire regarding intended breastfeeding duration, exclusivity, and perceptions, before intervention and at three, six, and twelve months post-partum. RESULTS: Fifty-two women with pre-gestational diabetes mellitus consented to participate. All completed the questionnaires, 26 in each group. At three, six, and twelve months postpartum, rates of any breastfeeding were around 60%, 50%, and 30%, respectively. Approximately one-third breastfed exclusively in each group at three and six months. No significant difference in breastfeeding rates was noted between face-to-face instruction, written information, and controls. End-of-pregnancy counseling improved confidence in breastfeeding knowledge and confidence in being able to manage blood glucose. CONCLUSIONS: Breastfeeding rates in pre-gestational diabetes mellitus were comparable to those of women without diabetes and were unchanged by mode of instruction at the end of pregnancy. However, targeted diabetes-oriented breastfeeding instruction at the end of pregnancy improved knowledge and confidence among women with pre-gestational diabetes mellitus.

Selective peripheral tissue response to high testosterone levels in an infertile woman without virilization signs.

Summary: Total testosterone, which is peripherally converted to its biologically active form dihydrotestosterone (DHT), is the first-line hormone investigation in hyperandrogenic states and infertility in premenopausal women. Polycystic ovary syndrome (PCOS), the most common cause of hyperandrogenism and infertility in young women, is often associated with mild elevations of total testosterone. Whereas very high levels of total testosterone (>2-3 SD of normal reference), are most often associated with hyperandrogenic signs, menstrual irregularity, rapid onset of virilization, and demand a prompt investigation. Herein, we report a case of a 32-year-old woman who was referred to the endocrinology outpatient clinic due to secondary amenorrhea and extremely high testosterone levels without any virilization signs. We initially suspected pitfalls in the testosterone laboratory test. Total serum testosterone decreased after a diethyl-ether extraction procedure was done prior to the immunoassay, but testosterone levels were still elevated. An ovarian steroid-cell tumor (SCT) was then revealed, which was thereby resected. Twenty-four hours post surgery, the total testosterone level returned to normal, and a month later menstruation resumed. This case emphasizes that any discrepancy between laboratory tests and the clinical scenario deserves a rigorous evaluation to minimize misinterpretation and errors in diagnosis and therapeutic approach. Additionally, we describe a possible mechanism of disease: a selective peripheral target-tissue response to high testosterone levels that did not cause virilization but did suppress ovulation and menstruation. Learning points: Total testosterone is the most clinically relevant hormone in investigating hyperandrogenic states and infertility in premenopausal women. Very high total testosterone levels in women (>2-3 SD of normal reference) are most often associated with hyperandrogenic signs, menstrual irregularities, and a rapid onset of virilization. In women with very elevated testosterone levels and the absence of clinical manifestations, laboratory interference should be suspected, and diethyl ether extraction is a useful technique when other methods fail to detect it. Ovarian steroid cell tumors (SCT) encompass a rare subgroup of sex cord-stromal tumors and usually secrete androgen hormones. SCTs are clinically malignant in 25-43% of cases. A selective response of peripheral target tissues to testosterone levels, with clinical manifestations in some tissues and no expression in others, may reflect differences in the conformation of tumor-produced testosterone molecules.

Prediabetes in pregnancy - follow-up, treatment, and outcomes compared to overt pregestational diabetes.

OBJECTIVE: There are limited data on follow-up, treatment, and maternal and fetal outcomes in women with prediabetes before or at the beginning of pregnancy. The aim of this study was to comprehensively characterize women with prediabetes compared to women with type 2 diabetes mellitus. STUDY DESIGN: This was a retrospective cohort data from a single medical center treating women with pregestational prediabetes mellitus (PDM). Women were compared to pregestational overt type 2 diabetes mellitus (T2DM). RESULTS: Data were collected from 120 women in the PDM group and 86 women in the T2DM group. Baseline characteristics were comparable, albeit women in the PDM group arrived at medical attention significantly later, 55% after 15 weeks gestation. Women with PDM needed significantly less treatment to achieve glycemic control and glycated hemoglobin remained lower throughout pregnancy. Maternal and fetal outcomes were similar between groups, although significantly higher rates of macrosomia and neonatal jaundice were observed in the T2DM group. CONCLUSIONS: The lack of clear guidelines causes a delay in the first prenatal visit of women with PDM. Comparable pregnancy outcomes may tip the balance toward acceptance of early treatment. Establishing clear guidelines will enable primary caregivers to refer prediabetic women sooner for lifestyle modifications and treatment if needed.

Adrenal metastatic melanoma first identified during pregnancy: a diagnostic challenge.

Adrenal nonadenomatous tumors (NAT) first identified during pregnancy are very rare and pose a diagnostic and therapeutic dilemma with significant risks for the mother and fetus. The aim of this study is to report a case of a large adrenal NAT identified in pregnancy and literature review. A literature search was conducted, and data were summarized. A 37-year-old primigravida woman, with a history of melanoma, excised 12 years before presentation without recurrence, presented at 35 weeks gestation due to intractable right flank pain. MRI demonstrated an eight cm, heterogeneous, septate, right adrenal mass suspected to be either pheochromocytoma/paraganglioma (PPGL), adrenocortical carcinoma or metastasis. Blood metanephrines were sent urgently to enable a safe delivery and were within normal range, as were cortisol and androgen levels. A biopsy was taken from a palpable breast mass as well as from an ovarian mass during the operation. At 36 weeks gestation, she was delivered by cesarean section. PET computed tomography performed after delivery revealed the extensive metastatic spread of recurring melanoma including the right adrenal gland. Timely diagnosis and management by a multidisciplinary team are important to avoid a catastrophic outcome. There is no consensus on optimal management and timing of delivery. PPGL should be ruled out before delivery.

Is Telemedicine the Preferred Visit Modality in Patients with Type 1 Diabetes?

BACKGROUND: The COVID-19 pandemic limits access to diabetes clinics. Remote communication by phone calls and WhatsApp messages became available in the past years. However, the current need to avoid face-to-face meetings necessitates further expansion of telemedicine services. There are limited data whether the option of virtual meetings is a preferred therapeutic modality for patients with type 1 diabetes (T1D). OBJECTIVE: To assess in a cohort of T1D patients, their preference and perception of telemedicine. METHODS: T1D patients who are followed in a hospital-affiliated diabetes clinic were asked to fill a structured questionnaire aimed to determine their attitude towards telemedicine and their preference of virtual versus conventional visits. The questionnaire was offered to consecutive T1D patients who visited the clinic between August to October 2020. RESULTS: Seventy one T1D patients that fulfilled the questionnaire were included. Median age was 38 years, 39% were male, and median duration of diabetes was 18 years. Fourteen percent of the participants preferred only virtual visits, 24% only conventional visits and 62% preferred a combination of these modalities. Sex, origin, education, duration of diabetes, mode of insulin treatment and distance from the clinic were not associated with patients' preference, but older patients (≥ 61 years) tended to prefer conventional visits. Sixty-six percent felt confident in their ability to download data from their personal medical devices. CONCLUSIONS: Patients from a wide range of treatment modalities are willing to use telemedicine. However, virtual meetings cannot fully replace conventional visits in T1D especially in the older age group.

The Challenges of Treating Glucokinase MODY during Pregnancy: A Review of Maternal and Fetal Outcomes.

Background: The optimal treatment strategy for the follow-up and management of women with glucokinase maturity-onset diabetes of the young (GCK−MODY)during pregnancy remains unknown. Data regarding maternal and fetal outcomes are lacking. Aim: This paper summarizes the existing literature regarding the maternal and fetal outcomes of women with glucokinase MODY to guide future treatment strategy. Methods: A literature search was conducted in Pubmed, Embace, and Cochrane library with citation follow-up using the terms: glucokinase, MODY, diabetes, pregnancy, gestation, and outcomes. We searched for articles with known fetal mutational status. Relevant outcomes included: birthweight, large for gestational age (LGA), small for gestational age (SGA), macrosomia, cesarean delivery (CD), shoulder dystocia, congenital anomalies, miscarriages, preterm births, and long-term outcomes. Results: Fourteen relevant manuscripts were identified describing maternal and fetal outcomes. The percentage of LGA and macrosomia in 102 glucokinase -unaffected offspring (GCK−) was significantly higher than in the glucokinase -affected offspring (GCK+) (44% vs. 10%, p < 0.001 and 22% vs. 2%, p < 0.001, respectively). Among the 173 GCK(+) offspring, only 5% were SGA, which can be expected according to the normal distribution. We observed higher rates of CD and shoulder dystocia in the GCK(−) offspring. Conclusions: GCK(−) offspring have significantly higher birthweights and more birth complications. The optimal treatment strategy to guide management should take into consideration multiple variables other than fetal mutational status.

Subacute Thyroiditis-Still a Diagnostic Challenge: Data from an Observational Study.

Background: Subacute thyroiditis (SAT) is a relatively common cause of thyroid disease. However, only a few studies evaluating SAT have been published in recent years with varying diagnostic criteria. We evaluate the clinical presentation and long-term outcome of isotope scan-confirmed SAT. Methods: A retrospective study of 38 patients with isotope scan-confirmed SAT was performed at a single isotope department. All patients were contacted for long-term follow-up. Results: The female/male ratio was 1.4:1, and mean age was 47 ± 14 years and 62 ± 12 years in women and men, respectively (p = 0.002). Almost half of the cases (42%) occurred during the summer. The most common symptoms were neck pain (74%) and weakness (61%). Palpitations, weight loss, heat intolerance, and sweating appeared in 50%, 42%, 21%, and 21%, respectively. Only half of the patients reported fever. TSH level was low in all patients, and mean FT4 and FT3 level were about twice the upper limit of normal range. Elevated CRP and ESR occurred in the majority (88%) of patients. The mean time period between the first clinic visit and performing thyroid function tests was 8 ± 7 days. One-third of the patients initially received a diagnosis of upper respiratory tract infection (URI). NSAIDs and steroids were prescribed to 47% and 8% of patients, respectively. Long-term follow-up of 33.5 months (range 9-52) revealed that 25% remained with subclinical or overt hypothyroidism. Conclusions: These data demonstrate that although SAT is a common entity, there is still a significant delay in diagnosis, and in a third of our patients, the initial diagnosis was URI, with 25% developing long-term hypothyroidism.

Severe post-gastric bypass hypoglycemia in pregnancy.

Post-bariatric surgery hypoglycemia (PBH) is a serious and relatively prevalent complication of bariatric surgery and is often underdiagnosed due to unawareness. PBH can have a profound effect on health and quality of life. Data regarding the natural history and management of PBH during pregnancy are lacking. Here we describe a case of a 34-year-old woman who presented with intractable PBH during the second trimester of her third pregnancy, three years after a Roux-en-Y gastric bypass (RYGB). Treatment with nifedipine showed partial response and eventually intravenous (IV) glucose was needed until birth.

Following the COVID-19 Experience, Many Patients with Type 1 Diabetes Wish to Use Telemedicine in a Hybrid Format.

BACKGROUND: The COVID-19 pandemic has brought to light both challenges and unique opportunities regarding type 1 diabetes (T1D) management, including the usage of telemedicine platforms. METHODS: This study was conducted in a tertiary hospital diabetes clinic. All consecutive T1D patients during March and June 2021 were asked to fill out a structured anonymous questionnaire that aimed to determine their preference regarding continuous use of a virtual platform. RESULTS: In total, 126 T1D patients answered the questionnaire, of whom 51% were under the age of 40, half were men, half used insulin pumps, and 69% used continuous glucose monitoring. During the pandemic, the exposure of patients to virtual visits has grown about twofold, from 29% to 53%. Of the respondents, 49% expressed an interest in future usage of a virtual platform, but most of them preferred use in a hybrid manner. We found an association between preference to use telemedicine in the future and younger age, previous virtual platform experience, and confidence in being able to download data. CONCLUSIONS: Our data demonstrate that the COVID-19 experience has led to a growing interest of T1D patients in using the hybrid format of telemedicine. However, we still need to better understand who will benefit most from this platform and assess its cost-effectiveness and organization.

Single liver metastasis of a follicular variant of papillary thyroid carcinoma: a rare pattern of organ spread.

SUMMARY: Well-differentiated thyroid cancer (WDTC), including papillary, follicular, and Hurthle-cell types, is characterized by a slow course and usually remain localized to the thyroid. However, a minority of these cases develop distant metastases with the most common sites being lungs, bones, and lymph nodes. Liver metastases of WDTC are rare and are usually found along with other distant metastases sites and in a multiple or diffuse pattern of spread. The recognition of distant metastasis in WDTC has a significant impact on the treatment and prognosis. However, because of their low incidence and awareness, distant metastases are often diagnosed late. Herein, we describe a case of a 71 years old woman who during routine surveillance of a follicular variant of papillary thyroid cancer (FV-PTC), 5 years after being treated for her primary thyroid tumor, was found to have a single liver metastasis and underwent liver segmental resection. This case highlights the importance of maintaining vigilant surveillance of patients with WDTC, and illustrates the possibility of unique metastasis at unexpected sites. Further studies are needed to understand the organ tropism of some WDTC leading to distant metastases development and to better prediction of an aggressive course. LEARNING POINTS: WDTC patients with distant metastases have a poor prognosis with a 10-year survival of about 50%. The most common sites of distant metastases are lung, bone and lymph nodes. Liver metastases are rare in WDTC, are usually multiple or diffuse and are found along with other distant metastases sites. Single liver metastasis of WDTC is an unexpected pattern of spread, and very few cases are reported in the literature. Rare sites of distant metastases in WDTC can manifest many years after the primary tumor, stressing the importance of maintaining vigilant surveillance. More studies are needed to predict which WDTC tumors may develop a more aggressive course, allowing clinicians to individualize patient management.