Papers by Henrik Falhammar
Endocrine, Apr 6, 2024
Purpose To study the prevalence of primary adrenal tumors and adrenal metastases in patients with... more Purpose To study the prevalence of primary adrenal tumors and adrenal metastases in patients with neuroendocrine neoplasms (NENs) and describe these in detail. NENs can be further divided into neuroendocrine tumor (NET) and neuroendocrine carcinoma (NEC). Methods A review of medical files was conducted for all patients who underwent a 68 Gallium-DOTATOC-PET/CT during 2010−2023 or adrenalectomy during 1999-2023 at the Karolinska University Hospital. Results In total, 68 Gallium-DOTATOC-PET/CT was performed on 1750 individuals with NEN, among whom 12 (0.69%) had adrenal tumors. Of these, 9 (0.51%) were NEN metastases. Out of 1072 adrenalectomies, 4 (0.37%) showed evidence of NEN metastases. Thus, 16 patients with NEN exhibited adrenal tumors. The adrenal tumors were found on average 5 years after the NEN diagnosis and 19% of the adrenal tumors with simultaneous NEN were benign. Few had all adrenal hormones measured. None had an adrenal insufficiency nor an adrenal biopsy. Another synchronous metastasis was found in 69% at the time of the adrenal tumor discovery. During the median 2-year follow-up, 38% of the subjects had deceased (with the exclusion of individuals presenting supposedly benign adrenal tumors 31%) all due to tumor complications. A comparison between individuals identified through 68 Gallium-DOTATOC-PET/CT and those who underwent adrenalectomy revealed a higher prevalence of NETs in the former group and NECs in the latter group. Conclusion Adrenal primary tumors and adrenal metastases are infrequent occurrences in patients with NEN. Most cases involved the presence of NEN metastasis upon the initial discovery of adrenal tumors. The overall prognosis was found to be favorable.
Cancers, Nov 15, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
European Journal of Internal Medicine, Nov 1, 2019
Background: Although tramadol and codeine occasionally have been reported to cause hyponatremia t... more Background: Although tramadol and codeine occasionally have been reported to cause hyponatremia the evidence is scarce. The objective of this investigation was to study the association between weak opioids (tramadol and codeine) and hospitalization due to hyponatremia. Methods: This was a register-based case-control study of the general Swedish population. Those hospitalized with a principal diagnosis of hyponatremia (n = 14,359) were compared with matched controls (n = 57,383). Multivariable logistic regression adjusting for co-medication, diseases, previous hospitalizations and socioeconomic factors was used to explore the association between severe hyponatremia and the use of tramadol or codeine. Furthermore, newly initiated (≤90 days) and ongoing use was investigated separately. Results: Compared to controls, the unadjusted OR (95%CI) for hospitalization due to hyponatremia was 2.45 (2.26-2.66) for tramadol and 3.19 (2.92-3.47) for codeine. However, after adjustment for confounding factors the risk decreased (adjusted OR: 1.17 [1.08-1.26] and 1.14 [1.03-1.26], respectively). Newly initiated treatment with tramadol or codeine showed a significant association (adjusted OR 2.34 [95%CI 2.01-2.72] and 2.20 [95%CI 1.87-2.60], respectively). In contrast, for ongoing therapy the corresponding adjusted ORs were not elevated (adjusted OR: 0.70 [95%CI 0.61-0.80] and 1.14 [95%CI 0.99-1.30, respectively). Conclusions: Associations were found between tramadol or codeine usage and hospitalization due to hyponatremia which were markedly increased in those newly initiated. The risk associated with long-term use was not increased. The association may be causally related to the drugs, although an effect due to pain, nausea or the underlying disease cannot be excluded.
Clinical Endocrinology, Sep 24, 2018
Results: There were 321 acute presentations among 74 children with CAH. Two thirds (66.7%, n=214)... more Results: There were 321 acute presentations among 74 children with CAH. Two thirds (66.7%, n=214) of these resulted in admission and 49.2% (n=158) of the patients received intravenous (IV) hydrocortisone. An AC was diagnosed in (9.0%). Prior to presentation, 64.2% (n=206) had used oral stress dosing and 22.1% (n=71) had been given intramuscular (IM) hydrocortisone. Vomiting was recorded in 61.1% (n=196), 32.7% (n=64) of whom had used IM hydrocortisone. Admission, AC diagnosis, and use of stress dosing varied significantly between hospitals. IM use varied from 7.0% in one metropolitan hospital to 45.8% in the regional hospital. Children aged up to 12 months had the lowest levels of stress dosing and IV hydrocortisone administration. A higher number of prior hospital attendances for acute illness was associated with increased use of IM hydrocortisone. Conclusion: Pre-hospital and in-hospital management of children with CAH can vary between health services. Children under 12 months have lower levels of stress dosing prior to hospital than other age groups. Experience with acute episodes improves self-management of CAH in the context of acute illness in educated patient populations.
Clinical Endocrinology, Jan 20, 2020
Background: In patients with congenital adrenal hyperplasia (CAH) type and doses of glucocorticoi... more Background: In patients with congenital adrenal hyperplasia (CAH) type and doses of glucocorticoids used as well as sex hormone secretion during puberty have important actions on bone mineral density (BMD) in adulthood. Aim: To evaluate BMD in adult CAH patients depending on current glucocorticoid therapy, and on androgen levels in adulthood and at age 16yrs. Methods: We included 244 CAH patients from the dsd-LIFE cohort (women n=147, men n=97; salt-wasting n=148, simple-virilizing n=71, non-classical n=25) in which BMD and bloods were available. Clinical and hormonal data at age 16yrs was retrieved from patients´ files. Results: Simple-virilizing women showed lower BMD compared to salt-wasting women at trochanter (0.65±0.12 vs 0.75±0.15 g/cm 2 ; p<0.050), whole femur T-score (-0.87±1.08 vs-0.16±1.24; p<0.05) and lumbar T-score (-0.81±1.34 vs 0.09±1.3; p<0.050). Fracture prevalence did not differ significantly between the CAH groups. Prednisolone vs. hydrocortisone only therapy caused worse trochanter Z-score (-1.38±1.46 vs-0.47±1.16; p<0.050). In women lumbar spine BMD correlated negatively with hydrocortisoneequivalent dose per body surface (r 2 =0.695, p<0.001). Furthermore, BMI at age 16yrs correlated positively with lumbar spine T-score (r 2 =0.439, p=0.003) and BMD (r 2 =0.420, p=0.002) in women. The androstenedione/testosterone ratio at age 16yrs correlated positively with lumbar spine Z-score in women (r 2 =0.284, p=0.024) and trochanter Zscore in men (r 2 =0.600, p=0.025). Conclusion: Higher glucocorticoid doses seemed to cause lower BMD especially in women. Prednisolone appeared to have more detrimental effects on BMD than hydrocortisone. Higher glucocorticoid doses (lower androstenedione/testosterone ratio) during adolescence may cause lower BMD in adulthood.
European Journal of Internal Medicine, Feb 1, 2019
Background: Antipsychotics have been claimed to cause hyponatremia. The risk associated with indi... more Background: Antipsychotics have been claimed to cause hyponatremia. The risk associated with individual antipsychotics, or groups (first-generation [FGAs] or second-generation [SGAs] antipsychotics), is not well-documented. The objective of this study was to investigate the association between antipsychotics and hospitalization due to hyponatremia. Methods: The general Swedish population was the base of this register-based case-control study. Comparisons were made between patients hospitalized with a principal diagnosis of hyponatremia (n = 14,359) and matched controls (n = 57,383). Multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and socioeconomic factors was performed to investigate the association between hyponatremia and antipsychotic use. In addition newly initiated (≤90 days) or ongoing use was analysed separately. Results: Compared to controls, the adjusted OR (95%CI) for hospitalization due to hyponatremia was for any antipsychotic 1.67(1.5-1.86). Individuals on FGA were more likely to experience severe hyponatremia (2.12[1.83-2.46]) than those on any SGA (1.32[1.15-1.51]). No increased risks, neither as newly initiated nor ongoing therapy, were found for risperidone (0.
Seizure-european Journal of Epilepsy, Jul 1, 2018
Hyponatremia induced by antiepileptic drugs is common, but detailed evidence is lacking. This can... more Hyponatremia induced by antiepileptic drugs is common, but detailed evidence is lacking. This can be problematic for the treating neurologist confronted with a patient with severe hyponatremia in need of an alternative drug. The objective of this study was to examine the association between individual antiepileptic drugs and hospitalization due to hyponatremia. Methods: This was a register-based case-control study of patients in the general Swedish population. We included 14,359 individuals with a principal diagnosis of hyponatremia and 57,383 matched controls. The association between newly initiated (90 days) and ongoing antiepileptic treatment was investigated using multivariable logistic regression adjusting for concomitant drugs, medical conditions, previous hospitalizations and sociaoeconomic factors. Results: For newly initiated antiepileptic drugs, adjusted ORs (95% CI) for hospitalization due to hyponatremia, compared to controls, were: carbamazepine 9.
European Journal of Internal Medicine, 2019
World Journal of Diabetes, 2016
Author contributions: All authors participated in the design of the literature search strategy an... more Author contributions: All authors participated in the design of the literature search strategy and eligibility criteria, approved the eligible references for inclusion in the review, reviewed and interpreted the extracted data from each publication, and were involved in the drafting, critical revision, and approval of the final version of the manuscript. Conflict-of-interest statement: Glynis P Ross has received financial support from AMSL, Medtronic, Eli Lilly, NovoNordisk, Sanofi, Novartis, and Merck Sharp and Dohme for the independent development and delivery of lectures; Henrik Falhammar has received research funding from the Magn. Bergvalls Foundation, Karolinska Institutet, and Stockholm County Council, and financial support from Boehringer Ingelheim, AstraZeneca, Merck Sharp and Dohme, Sanofi, NovoNordisk, and Ipsen for delivery of lectures; Roger Chen has received financial support from and/or served on advisory boards for Novo Nordisk, Merck Sharp and Dohme, Novartis, AstraZeneca, and Janssen Cilag, and received an educational grant from Boehringer Ingelheim; Helen Barraclough is an employee of, and Ole Kleivenes is a former employee of, Eli Lilly Australia and New Zealand; Ian Gallen has received speaker fees from Eli Lilly and NovoNordisk, and provides educational events for patients and healthcare professionals, funded by Animas Corporation and Eli Lilly, respectively. Data sharing statement: This article is a systematic review of the literature and did not include a meta-analysis; as such, all reported data are derived from the published articles and data sharing is not relevant.
International Journal of Endocrinology, 2018
Magnesium is the fourth most abundant cation in the body. It has several functions in the human b... more Magnesium is the fourth most abundant cation in the body. It has several functions in the human body including its role as a cofactor for more than 300 enzymatic reactions. Several studies have shown that hypomagnesemia is a common electrolyte derangement in clinical setting especially in patients admitted to intensive care unit where it has been found to be associated with increase mortality and hospital stay. Hypomagnesemia can be caused by a wide range of inherited and acquired diseases. It can also be a side effect of several medications. Many studies have reported that reduced levels of magnesium are associated with a wide range of chronic diseases. Magnesium can play important therapeutic and preventive role in several conditions such as diabetes, osteoporosis, bronchial asthma, preeclampsia, migraine, and cardiovascular diseases. This review is aimed at comprehensively collating the current available published evidence and clinical correlates of magnesium disorders.
Yearbook of pediatric endocrinology, Oct 23, 2020
Context P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with ... more Context P450 oxidoreductase deficiency (PORD) is a rare genetic disorder that is associated with significant morbidity. However there has been limited analysis of reported PORD cases. Objective To determine, based on the cohort of reported PORD cases, genotype-phenotype relationships for skeletal malformations, maternal virilisation in pregnancy, adrenal insufficiency and disorders of sexual development (DSD).
The New Zealand Medical Journal, Jun 6, 2008
Frontiers in Endocrinology, Nov 18, 2022
Molecular Diagnosis & Therapy, Apr 27, 2022
The term CAH-X was coined to describe a subset of patients with 21-hydroxylase deficiency display... more The term CAH-X was coined to describe a subset of patients with 21-hydroxylase deficiency displaying a phenotype compatible with the hypermobility type of Ehlers Danlos syndrome. The genetic defect is due to the monoallelic presence of a CYP21A2 deletion extending into the gene encoding tenascin X (TNXB), a connective tissue extracellular matrix protein. The result is a chimeric TNXA/TNXB gene causing tenascin-X haploinsufficiency. The prevalence of CAH-X was estimated to be around 14-15% in large cohorts of patients with 21-hydroxylase deficiency. However, population studies are still scarce and the clinical picture of the syndrome has yet to be fully defined. In this review, we discuss the current knowledge regarding the genetic and clinical profile of the CAH-X syndrome.
Journal of Psychopharmacology, Jul 20, 2020
Background: Many drugs used in psychiatry have been reported to cause hyponatraemia. However, lit... more Background: Many drugs used in psychiatry have been reported to cause hyponatraemia. However, lithium may be an exception due to its potential for causing nephrogenic diabetes insipidus, but clinical data are largely absent. The objective of this investigation was to study the association between lithium therapy and hospitalization due to hyponatraemia. Methods: This study was a register-based case-control investigation of the general Swedish population. Patients hospitalized with a principal diagnosis of hyponatraemia (n=11,213) were compared with matched controls (n=44,801). Analyses using multivariable logistic regression adjusting for comedication, diseases, previous hospitalizations and socioeconomic factors were deployed to calculate the association between severe hyponatraemia and the use of lithium. Additionally, newly initiated (⩽90 days) and ongoing lithium therapy was studied separately. Results: Compared with controls, the unadjusted odds ratio (OR) (95% confidence interval (CI)) for hospitalization due to hyponatraemia was 1.07 (0.70-1.59) for lithium. However, after adjustment for confounding factors the risk was reduced (adjusted OR: 0.53 (0.31-0.87)). Newly initiated lithium therapy was not significantly associated with hyponatraemia (adjusted OR 0.73 (0.35-5.38)). In contrast, for ongoing therapy the corresponding adjusted OR was significantly reduced (adjusted OR: 0.52 (0.30-0.87)). Conclusions: A marked inverse association was found between ongoing lithium therapy and hospitalization due to hyponatraemia.
BMJ Open, May 1, 2022
Objectives To assess the prevalence and incidence of diabetes among Aboriginal peoples in remote ... more Objectives To assess the prevalence and incidence of diabetes among Aboriginal peoples in remote communities of the Northern Territory (NT), Australia. Design Retrospective cohort analysis of linked clinical and administrative data sets from 1 July 2012 to 30 June 2019. Setting Remote health centres using the NT Government Primary Care Information System (51 out of a total of 84 remote health centres in the NT). Participants All Aboriginal clients residing in remote communities serviced by these health centres (N=21 267). Primary outcome measures Diabetes diagnoses were established using hospital and primary care coding, biochemistry and prescription data. Results Diabetes prevalence across all ages increased from 14.4% (95% CI: 13.9% to 14.9%) to 17.0% (95% CI: 16.5% to 17.5%) over 7 years. Among adults (≥20 years), the 2018/2019 diabetes prevalence was 28.6% (95% CI: 27.8% to 29.4%), being higher in Central Australia (39.5%, 95% CI: 37.8% to 41.1%) compared with the Top End region (24.2%, 95% CI: 23.3% to 25.1%, p<0.001). Between 2016/2017 and 2018/2019, diabetes incidence across all ages was 7.9 per 1000 person-years (95% CI: 7.3 to 8.7 per 1000 person-years). The adult incidence of diabetes was 12.6 per 1000 person-years (95% CI: 11.5 to 13.8 per 1000 person-years). Conclusions The burden of diabetes in the remote Aboriginal population of the NT is among the highest in the world. Strengthened systems of care and public health prevention strategies, developed in partnership with Aboriginal communities, are needed.
Australian & New Zealand Journal of Obstetrics & Gynaecology, Mar 8, 2013
Background: Australian Aboriginal women have a high prevalence of type 2 diabetes (T2DM) in pregn... more Background: Australian Aboriginal women have a high prevalence of type 2 diabetes (T2DM) in pregnancy and gestational diabetes (GDM). Aims: To review how screening practice affects the pregnancy data of all Indigenous women and their newborns living in Cape York, Queensland. Methods: All medical charts of mothers and their neonates delivered in the regional hospital over two-one-year periods (2006 and 2008) were reviewed. Universal testing with an oral glucose tolerance test (OGTT) was introduced in 2007. Results: Gestational diabetes (GDM) increased from 4.7 to 14.2%, and T2DM was similar (2.4 and 2.3%). There were 127 deliveries in 2006 and 134 in 2008. Testing rates with OGTT improved from 31.4% in 2006 to 65.6% in 2008. Mothers with diabetes in pregnancy (DIP) were older and heavier than non-DIP mothers. Caesarean section rates were significantly higher in the DIP group compared with the non-DIP group (66 vs 25%) in both time periods. The booking weight of DIP mothers decreased 16 kg, their babies normalised their weight, length and head circumference; respiratory distress and Apgar scores improved comparing the two periods. In DIP, infants >40% had hypoglycaemia; however, rates of serious complications were low. Rates of breastfeeding were similar between groups. Follow-up rates for GDM improved from 16.6% in 2006 to 31.6% in 2008. Of those tested one-third were diagnosed with T2DM. Conclusion: The rate of GDM tripled after implementation of universal testing. Outcomes improved. There is still need for improvement in testing and follow-up practices in relation to DIP.
European Journal of Internal Medicine, Oct 1, 2021
The American Journal of Medicine, Apr 1, 2021
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Papers by Henrik Falhammar