Hypercalcemic crisis in third trimenon: evaluating the optimal treatment strategy

Hypercalcemia due to primary hyperparathyroidism during pregnancy is a rare condition and associated with increased morbidity and mortality for the mother and the unborn child. Whereas parathyroidectomy is favored during the second trimester, no clear recommendations exist for its management during the third trimenon. We here report the case of a 26-year-old woman in the 29th week of her first pregnancy, who was admitted to our clinic with hypertension, intra-uterine growth retardation and polyhydramnios. Severe hypercalcemia due to primary hyperparathyroidism was diagnosed (total calcium 3.34?mmol/l; PTH 216?pg/ml), but no enlarged parathyroid gland could be localized by ultrasound. Treatment with calcitonin and cinacalcet could not control hypercalcemia. Therefore explorative surgery was performed and a single parathyroid adenoma was resected, resulting in normalization of serum calcium levels. The surgical procedure was tolerated well by the mother and fetus. Hypercalcemia-induced hypertension and polyhydramnios ameliorated before C-section was performed two weeks later and unrelated to the intervention. This case report underlines the importance of early diagnosis and treatment of primary hyperparathyroidism during pregnancy. If diagnosed in the third trimenon, an interdisciplinary approach is crucial. If medical treatment fails to sufficiently control hypercalcemia, surgical parathyroid exploration should be considered even in cases of unsuccessful localization of adenomatous parathyroid glands.     

The effect of glucose dynamics on plasma copeptin levels upon glucagon,arginine, and macimorelin stimulation in healthy adults

Pituitary - Non-osmotic stimulation tests using glucagon, arginine, or macimorelin were recently evaluated for their ability to assess posterior pituitary function. Glucagon and arginine, but not...     

Theranostics in neuroendocrine tumors: an overview of current approaches and future challenges

Reviews in Endocrine and Metabolic Disorders - Neuroendocrine neoplasms (NENs) comprise a heterogeneous group of tumors, mainly localized in the gastrointestinal system. What characterizes NENs is...     

Diagnosis and management of diabetes insipidus for the internist: an update

Diabetes insipidus is a disorder characterized by excretion of large amounts of hypotonic urine. Four entities have to be differentiated: central diabetes insipidus resulting from a deficiency of the hormone arginine vasopressin (AVP) in the pituitary gland or the hypothalamus, nephrogenic diabetes insipidus resulting from resistance to AVP in the kidneys, gestational diabetes insipidus resulting from an increase in placental vasopressinase and finally primary polydipsia, which involves excessive intake of large amounts of water despite normal AVP secretion and action. Distinguishing between the different types of diabetes insipidus can be challenging. A detailed medical history, physical examination and imaging studies are needed to detect the aetiology of diabetes insipidus. Differentiation between the various forms of hypotonic polyuria is then done by the classical water deprivation test or the more recently developed hypertonic saline or arginine stimulation together with copeptin (or AVP) measurement. In patients with idiopathic central DI, a close follow-up is needed since central DI can be the first sign of an underlying pathology. Treatment of diabetes insipidus or primary polydipsia depends on the underlying aetiology and differs in central diabetes insipidus, nephrogenic diabetes insipidus and primary polydipsia. This review will discuss issues and newest developments in diagnosis, differential diagnosis and treatment, with a focus on central diabetes insipidus.     

A randomized controlled trial of the GLP-1 receptor agonist dulaglutide in primary polydipsia

BackgroundPrimary polydipsia, characterized by excessive fluid intake, carries the risk of water intoxication and hyponatremia, but treatment options are scarce. Glucagon-like peptide 1 (GLP-1) reduces appetite and food intake. In experimental models, GLP-1 has also been shown to play a role in thirst and drinking behavior. The aim of this trial was to investigate whether GLP-1 receptor agonists reduce fluid intake in patients with primary polydipsia.MethodsIn this randomized, double-blind, placebo-controlled, 3-week crossover trial, 34 patients with primary polydipsia received weekly dulaglutide (1.5 mg, Trulicity) in one treatment segment and placebo (0.9% sodium chloride) in the other. During the last treatment week, patients attended an 8-hour evaluation visit with free access to water. The primary endpoint was total fluid intake during the evaluation visits. Treatment effects were estimated using linear mixed-effects models. In a subset of 15 patients and an additional 15 matched controls, thirst perception and neuronal activity in response to beverage pictures were assessed by functional MRI.RESULTsPatients on dulaglutide reduced their fluid intake by 490 mL (95% CI: –780, –199; P = 0.002), from 2950 mL (95% CI: 2435, 3465) on placebo to 2460 mL (95% CI: 1946, 2475) on dulaglutide (model estimates), corresponding to a relative reduction of 17%. Twenty-four-hour urinary output was reduced by –943 mL (95% CI: –1473, –413; P = 0.001). Thirst perception in response to beverage pictures was higher for patients with primary polydipsia than for controls, and lower for patients on dulaglutide versus placebo, but functional activity was similar among groups and treatments.CONCLUSIONSGLP-1 receptor agonists reduce fluid intake and thirst perception in patients with primary polydipsia and could therefore be a treatment option for these patients.Trial registrationClinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT02770885","term_id":"NCT02770885"}}NCT02770885.FundingSwiss National Science Foundation (grant 32473B_162608); University Hospital and University of Basel; Young Talents in Clinical Research grant from the Swiss Academy of Medical Sciences and the Gottfried & Julia Bangerter-Rhyner Foundation; Top-up Grant from the PhD Programme in Health Sciences, University of Basel.     

Copeptin and its role in the diagnosis of diabetes insipidus and the syndrome of inappropriate antidiuresis

Copeptin is secreted in an equimolar amount to arginine vasopressin (AVP) but can easily be measured in plasma or serum with a sandwich immunoassay. The main stimuli for copeptin are similar to AVP, that is an increase in osmolality and a decrease in arterial blood volume and pressure. A high correlation between copeptin and AVP has been shown. Accordingly, copeptin mirrors the amount of AVP in the circulation. Copeptin has, therefore, been evaluated as diagnostic biomarker in vasopressin‐dependent disorders of body fluid homeostasis. Disorders of body fluid homeostasis are common and can be divided into hyper‐ and hypoosmolar circumstances: the classical hyperosmolar disorder is diabetes insipidus, while the most common hypoosmolar disorder is the syndrome of inappropriate antidiuresis (SIAD). Copeptin measurement has led to a “revival” of the direct test in the differential diagnosis of diabetes insipidus. Baseline copeptin levels, without prior thirsting, unequivocally identify patients with nephrogenic diabetes insipidus. In contrast, for the difficult differentiation between central diabetes insipidus and primary polydipsia, a stimulated copeptin level of 4.9 pmol/L upon hypertonic saline infusion differentiates these two entities with a high diagnostic accuracy and is clearly superior to the classical water deprivation test. On the contrary, in the SIAD, copeptin measurement is of only little diagnostic value. Copeptin levels widely overlap in patients with hyponatraemia and emphasize the heterogeneity of the disease. Additionally, a variety of factors lead to unspecific copeptin elevations in the acute setting further complicating its interpretation. The broad use of copeptin as diagnostic marker in hyponatraemia and specifically to detect cancer‐related disease in SIADH patients can, therefore, not be recommended.