Birgit Harbeck

No stress after 24-hour on-call shifts?

No stress after 24‐hour on‐call shifts? : Birgit Harbeck, et al. Department of Medicine I, University of Luebeck, Germany

Tumor-induced osteomalacia: successful treatment by radio-guided tumor surgery.

Tumor-induced osteomalacia is a rare syndrome characterized by urinary phosphate loss with hypophosphatemic osteomalacia. The proposed pathogenetic mechanism is paraneoplastic secretion of phosphaturic factors (so-called phosphatonins).We describe a 34-year-old male patient who presented with severe pain of the spine and ribs for at least 2 years. Bone scintigraphy using 99mTechnetium hydroxymethylene diphosphonate (99mTc HDP) showed multiple lesions suggesting metastatic disease. Bone biopsy however revealed osteomalacia. The patient had subnormal plasma phosphate levels (0.42 mmol/L; normal range, 0.87–1.45) and markedly increased phosphate clearance (82.8 mL/min; normal range, 5.4–16.2). The patient was treated with phosphate supplementation (up to 5 g daily) along with calcium (1000 mg daily) and calcitriol (1.5 &mgr;g daily). Although this therapy did not correct hypophosphatemia, it resulted in complete relief of pain within several months.111In pentetreotide scintigraphy showed a tiny lesion of 1-cm diameter, which could be localized to the left femoral neck in close vicinity to the greater trochanter by MRI and image fusion analysis. This lesion had not been visualized by Tc-99m HDP bone scintigraphy. Intraoperatively, use of a hand-held gamma probe after administration of 111Indium pentetreotide (111In pentetreotide) clearly identified the tumor, which was completely removed and was shown to be a hemangiopericytoma. After removal of the tumor, phosphate metabolism normalized within 1 week without requirement of phosphate supplementation.Hypophosphatemic osteomalacia, although rare, raises an important differential diagnosis. An underlying tumor may be detected only by 111In pentetreotide scintigraphy. Preoperative labeling with 111In pentetreotide is a useful tool in detecting these tumors during surgery.This 34 year old man with osteomalacia had a small causative hemangiopericytoma detected in the 111indium pentetreotide scintography.

Low-dose tolvaptan for the treatment of hyponatremia in the syndrome of inappropriate ADH secretion (SIADH)

The syndrome of inappropriate ADH secretion (SIADH) is most commonly drug induced or results from paraneoplastic secretion of antidiuretic hormone (ADH) by numerous cancer types, with small cell lung cancer (SCLC) being the most common tumor type. In addition, other causes such as septicaemia, pulmonary, or cerebral disorders may [1] stimulate ADH/vasopressin secretion, impair free water clearance, and subsequently induce hyponatremia. The resulting misbalance between sodium and water may be associated with uncharacteristic symptoms such as nausea, vomiting, unstable gait, vertigo, disorientation, and impairment of cognitive functions but—depending on the severity of the electrolyte disorder and the velocity of development—can also present with severe neurological signs, such as seizures and loss of consciousness [2]. Finally, hyponatremia has been shown to be associated with higher mortality [3]. Conventional treatment of SIADH with mild to moderate reduced sodium levels consists of fluid restriction and rarely demeclocycline or urea, whereas administration of hypertonic saline is used in symptomatic severe cases of hyponatremia [2]. Fluid restriction is a cumbersome procedure and often fails to achieve long-term results in part due to lack of patient compliance [4]. As long-term treatment is required when the underlying cause cannot successfully be corrected, better therapeutic options were urgently needed. The orally active drug tolvaptan, which acts as a vasopressin receptor subtype 2 antagonist and directly acts on the ADH target, is such a development as it is able to rapidly and effectively improve hyponatremia [5]. Although the lowest formally approved dose of tolvaptan is currently 15 mg/day, there is concern that a single dose of 15 mg tolvaptan may too rapidly increase the serum sodium level, thereby leading to neurological alterations, including cerebral pontine myelinolysis, a severe and often fatal neurological complication [6]. Clinical experience suggested that some patients are very susceptible to tolvaptan and that lower doses may also be sufficient to normalize hyponatremia [7]. To address this issue, we retrospectively analyzed a series of 37 patients (13 males, 24 females, age 55–93 years, median 77 years) treated with tolvaptan for SiADH. The diagnosis of SIADH in euvolemic hyponatremia patients was based on classical Bartter’s criteria where available (decreased plasma osmolality, urine osmolality[100 mOsmol/kg, urinary sodium above 30 mmol/L). The majority of SIADH cases (43 %) were tumor-associated, 19 % had a cerebral or pulmonary cause, and 14 % were drug induced. The remaining quarter was classified as idiopathic SIADH. A total of 15 patients had been initially treated with the lowest formally approved dose of 15 mg tolvaptan, whereas 22 were started on 7.5 mg tolvaptan daily. These groups did not significantly differ with respect to age, sex, and serum sodium levels obtained on hospital admission (Table 1). Tolvaptan was prescribed by several physicians with no specific dose preference of either of them. An initial fluid challenge with isotonic saline was performed in 12/15 patients (80 %) in the normal tolvaptan group and in 19/22 patients (86 %) in the low-tolvaptan group. Fluid restriction as initial treatment was prescribed in only three patients of the 15 mg group. Despite baseline sodium values prior tolvaptan administration tending to be higher in the 7.5 mg group (124.0 ± 3.7 vs. 120.4 ± 6.4 mEq/L, p = 0.057), sodium change within 24 and 48 h following the first dose of & Christian S. Haas cs_haas@yahoo.com

Hyponatremia Due to Thyrotropin Deficiency: A Fairy Tale?

on hemoglobin A1c, total cholesterol, low-density lipoprotein cholesterol, and triglycerides were also seen in the ITT population (a more conservative analysis). Drs Chirapongsathorn and Anthanont point out that nausea, vomiting, and diarrhea are common adverse effects when patients initiate exenatide treatment. Thesemost common adverse events reported with exenatide are typically mild, transient, and occur primarily in the early weeks of therapy, as supported by the exposure-adjusted event rates for gastrointestinal tracte related adverse events presented in the Table in our article, which were substantially lower during the open-label extension phase of the study compared with the initial 30-week controlled phase. Drs Chirapongsathorn and Anthanont also commented about the use of ITT analysis when a substantial proportion of patients have discontinued treatment. For this reason, efficacy data were presented for the completer population, supplemented by an ITT analysis. The consistency of these 2 analyses supports the general observations regarding the efficacy of exenatide once weekly. We agree with Drs Chirapongsathorn and Anthanont that randomized, controlled trial data are important to fully assess treatment efficacy and safety, although the challenges of patient recruitment and continuation as well as costs associated with longterm studies are compounded when conducting controlled studies. The lack of a control group is noted in the “Discussion” section of our article as a potential limitation of the current study that limits comparisons with other treatments and with the contribution of the progressive nature of type 2 diabetes. However, we also noted that the DURATION-3 study compared exenatide once weekly with an active control group (insulin glargine) for 3 years. In that study, patients receiving exenatide once weekly (when compared with patients

Increased Cardiovascular Risk in Patients with Adrenal Insufficiency: A Short Review

Cardiovascular disease (CVD) is the most common cause of death in the world. Recent studies have shown an association between adrenal insufficiency (AI) and increased cardiovascular risk (CVR). Patients with AI receive glucocorticoid (GC) replacement therapy which can lead to varying levels of blood cortisol. It was shown that these imbalances in blood cortisol may lead to a higher prevalence of coronary heart disease, major adverse coronary events, and increased mortality. GC substitution is essential in the treatment of AI without which the disease has been shown to be fatal. The most frequently used GC formula for replacement therapy is hydrocortisone (HC). There is no uniform opinion on hydrocortisone replacement therapy. Alternative GC such as prednisolone is also in use. Overreplacement of GC may lead to adverse effects including obesity, high blood pressure, and hyperglycaemia. Outcome may vary between primary and secondary AI mainly due to differences in the renin-angiotensin-aldosterone system (RAAS). Furthermore, decreased blood levels of cortisol may lead to a compensatory secretion of inflammatory mediators such as Interleukin-1 (IL-1), Interleukin-6 (IL-6), and/or tumor-necrosis factor (TNF). Physicians and patients should be properly educated about the increased risk of CVD in patients with AI.

Cardiac myopathy due to overt hypothyroidism

HISTORY AND ADMISSION FINDINGS A 51-year-old man presented with progressive tiredness, proximal muscle weakness, hair loss and weight gain for months. The patient showed mild pretibial myxedema and dry skin. Laboratory findings revealed strongly elevated cardiac enzymes as well as marked hypothyroidism. INVESTIGATIONS The electrocardiogram, echocardiography, abdominal sonography and chest X-ray were unremarkable. Thyroid ultrasound demonstrated features of Hashimoto thyroiditis. TREATMENT AND COURSE The findings supported the diagnosis of an overt hypothyroidism with myxedema and rhabdomyolysis. After starting levothyroxine and volume substitution laboratory parameters and clinical condition slowly normalized. CONCLUSION Severe overt hypothyroidism may rarely present primarily as myopathy with myositis and cardiac involvement.

A hypertensive patient presenting with paraneoplastic perimyocarditis and myositis due to pheochromocytoma

Hypertension is a frequent condition in the general population, and may lead to severe end organ damage. Various endocrine disorders cause hypertension, requiring specific attention and treatment. Paragangliomas (PGLs) are catecholamine producing chromaffin cell tumors developing from the sympathetic and parasympathetic ganglia throughout the abdomen and head and neck area, respectively. When arising from the adrenal gland, PGLs are referred to as pheochromocytomas (PHEOs). PGLs/PHEOs have an incidence of 1–2 per 100,000 and a prevalence of 0.1–0.4% in patients with hypertension [1]. They synthesize and secrete catecholamines and more rarely dopamine, causing a variety of clinical symptoms. The classic triad of symptoms consists of episodic headache (90%), sweating (60–70%) and heart palpitations. Moreover, most patients with PGL/PHEO suffer from paroxysmal or sustained hypertension. However, 5–15% of patients present with normal blood pressure. Other symptoms might be dyspnea, weakness, weight loss, psychiatric disorders or alterations in carbohydrate metabolism (hyperglycemia, insulin resistance). Several genetic disorders are associated with PHEOs (MEN 2a/b, von Hippel– Lindau disease, SDH gene mutations, MAXmutations, Neurofibromatosis Type 1). We here report the case of a hypertensive patient with a PHEO presentation with myositis and perimyocarditis. A 76 year-old female patient with a history of hypertension was admitted to the hospital with progressive severe pain and weakness of the shoulder girdle and thighs for several weeks. Laboratory

Diagnostik und Therapie der Nebenniereninsuffizienz

Adrenal insufficiency is a potentially life-threatening endocrine disorder. Therefore, it is very important to detect the symptoms in sufficient time and treat effectively to avoid acute adrenal insufficiency. This article provides an insight into diagnostically procedures and therapeutically specific aspects of this rare endocrine disease.

Prevalence and predictors of overweight and obesity in patients with pituitary dysfunctions

BACKGROUND Patients with hypothalamic-pituitary disorders (HPD) may be of increased risk to develop overweight and obesity, thereby fostering cardiovascular events. However, it remains unclear if patients with pituitary dysfunctions per se have an increased risk of becoming obese. OBJECTIVE The objective of this study was to evaluate prevalence and to identify possible predictors of overweight and obesity in patients with pituitary dysfunctions. METHODS A total of 121 out-patients having various causes for HPD were assessed for height and body weight; body mass index (BMI) was calculated and correlated with clinical features. Patients were divided into various subgroups depending on underlying conditions and therapeutic modalities. RESULTS Most of the HPD patients were overweight or obese with males being significantly more affected. Of interest, patients with macroadenomas suffered significantly more often from overweight and obesity than individuals with microadenomas (73.4% vs. 43.5%, p= 0.006). Increased BMI (≥25 kg/m2) tended to be more common in patients with prolactinomas (70.0%), hormone deficiencies (76.1%) and hormone replacement therapies (76.6%) than in a healthy population. CONCLUSION In conclusion, we showed that patients with HPD: (i) frequently suffer from overweight and obesity; (ii) prevalence of overweight and obesity however is comparable to that in the general population; (iii) only patients with macroadenomas seem to have a significantly higher risk; (iv) hormone deficiencies and hormonal replacement therapy may foster weight gain and (v) radiation and surgical tumour therapy per se do not seem to be additional risk factors for weight gain.

Experience pays off! Endocrine centres are essential in the care of patients with adrenal insufficiency

Patients with adrenal insufficiency (AI) require continuous glucocorticoid (GC) replacement treatment to restore well-being and to prevent life-threatening complications. Knowledge of symptoms of inadequate replacement and on therapeutic options is of utmost importance to provide best medical care. We previously demonstrated significant differences between physicians working at Hospitals with and without a Division of Endocrinology when asked about knowledge of clinical signs and treatment of AI [1]. Thereforewe assumed that physicians, who have more frequently contact with AI patients, are better informed and that personal experience might have a major impact on management of AI patients. Data from a previous paper-based survey of 209 physicians on physiological aspects on cortisol, glucocorticoid substitution therapy and symptoms of inadequate replacement in AI patients [1] were used for a subgroup analysis. We evaluated the impact of earlier encounters with AI patients on quality of treatment in this patient group. Therefore we analysed 120 questionnaires obtained from physicians working in Internal Medicine Departments at ten hospitals in Germany, four of them equipped with a Division of Endocrinology. Depending on their previous experience with AI patients, physicians were allocated to groups: a) Little expertise: never treated an AI-patient; b)Moderate expertise: treated at least one but less than 10 patients; and c) Large expertise: treated more than 10 patients. Chi-quadrat test was used to determine differences. P-value b 0.05 was considered to be significant. Twenty-seven physicians belonged to the groupwith little, 59 to the one with moderate expertise and 34 physicians were regarded as doctors with large expertise. Among the latter half of the physicians were seniors, the majority (85%) was working at a hospital with a Division of Endocrinology on-site. The results are shown in Table 1. Altogether 3/4 of the answers were correct, colleagues with little expertise scored worst. All groups scored insufficiently in basic information about adrenal insufficiency. Less than 1/2 of all interviewed physicians (45%) were aware of the correct cortisol production rate. The short lasting effect of hydrocortisone was rated correctly only by 1/4 of all participants. Upon asking for the various drugs for substitution therapy, only 50% correct answers were given: Physicians of the little expertise (39% correct answers) andmoderate group (48% correct answers) were significantly less informed than physicians with large expertise (63% correct answers). These