Eigil Husted Nielsen

Excess mortality in women with pituitary disease: a meta-analysis

Background  Increased mortality has been reported in patients with pituitary disease, with some studies showing higher standard mortality rates (SMR) in women than in men.

Craniopharyngioma: historical notes

For centuries tumors have been described which today with some confidence can be diagnosed as craniopharyngiomas. It was not until 1904 Erdheim described what he called ‘hypophysial duct tumors’, and which Cushing later gave the name craniopharyngioma. The first operation for this neoplasm took place in 1909. It soon became evident that the outcome of surgery was rather dismal with high mortality and morbidity rates—even after corticosteroid therapy became available around 1950. Radiotherapy was introduced and later refined as radiosurgery. This paper presents a short survey of the accumulation of knowledge of craniopharyngiomas.

Pregnancy outcomes in women with growth hormone deficiency

OBJECTIVE To study pregnancies in a large group of patients with growth hormone deficiency and hypopituitarism; and to investigate potential factors determining pregnancy outcomes and pregnancy complications. DESIGN We analyzed pregnancies reported in KIMS, the Pfizer International Metabolic Database, of adult patients with growth hormone deficiency treated with growth hormone. SETTING Outpatient clinics. PATIENT(S) A total of 201 pregnancies were reported: 173 in female patients and 28 in partners of male patients. INTERVENTION(S) Growth hormone replacement therapy (GHRT) was prescribed according to the local clinical practice. MAIN OUTCOME MEASURE(S) Pregnancy outcomes (live births, gestational week at delivery, and birth weight), pregnancy complications, and their relationship to use of GHRT during pregnancy were analyzed with regression models. RESULT(S) Two-thirds of women underwent fertility treatment to achieve pregnancy. Growth hormone replacement therapy was stopped before pregnancy in 7.5% of the female patients, as soon as pregnancy was confirmed in 40.1%, and at the end of the second trimester in 24.7% of the patients, whereas 27.6% continued GHRT throughout pregnancy. Birth of a healthy child was reported in 79% of the female pregnancies, nonelective abortions occurred mainly in the first trimester, and one fetal malformation (cystic hygroma) was diagnosed in the second trimester. Pregnancy outcomes and pregnancy complications were not related to GHRT treatment patterns, method of conception, or number of additional pituitary deficiencies. CONCLUSION(S) These data on pregnancy outcomes in a large group of women with hypopituitarism revealed no relationship between GHRT regimens and pregnancy outcomes.

Incidence of neuromyelitis optica spectrum disorder in the Central Denmark Region.

Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) may be misdiagnosed as multiple sclerosis. The aim of this study was to (i) to measure AQP4‐IgG in patients who fulfilled the clinical and radiological criteria of NMOSD in the Central Denmark Region and (ii) to estimate the incidence of NMOSD in the region, according to both the 2006 Wingerchuk criteria and the 2015 International Panel for NMO Diagnosis criteria.

Carcinoid syndrome caused by a serotonin-secreting pituitary tumour

BACKGROUND Neuroendocrine tumours are most frequently located in the gastrointestinal organ system or in the lungs, but they may occasionally be found in other organs. CASE We describe a 56-year-old woman suffering from a carcinoid syndrome caused by a large serotonin-secreting pituitary tumour. She had suffered for years from episodes of palpitations, dyspnoea and flushing. Cardiac disease had been suspected, which delayed the diagnosis, until blood tests revealed elevated serotonin and chromogranin A in plasma. The somatostatin receptor (SSR) scintigraphy showed a single-positive focus in the region of the pituitary gland and MRI showed a corresponding intra- and suprasellar heterogeneous mass. After pre-treatment with octreotide leading to symptomatic improvement, the patient underwent trans-cranial surgery with removal of the tumour. This led to a clinical improvement and to a normalisation of SSR scintigraphy, as well as serotonin and chromogranin A levels. CONCLUSION To our knowledge, this is the first reported case of a serotonin-secreting tumour with a primary location in the pituitary.

Acromegaly according to the Danish National Registry of Patients: how valid are ICD diagnoses and how do patterns of registration affect the accuracy of registry data?

Background The incidence of acromegaly is uncertain, since population-based studies are few. In the absence of a specific acromegaly registry, the Danish National Registry of Patients (DNRP) becomes a potential source of data for studying the epidemiology of acromegaly, by linking all hospital discharge diagnoses to the personal identification numbers of individual Danish inhabitants. The validity of the DNRP with respect to acromegaly, however, remains to be tested. The aim of this study was to validate the International Classification of Diseases (ICD) codes for acromegaly (ICD-8: 25300, 25301. ICD-10: E22.0) as used in the DNRP, and to assess the influence of various registration patterns on the accuracy of registry data. Methods We identified patients registered with ICD codes for the diagnosis of acromegaly or other pituitary disorders during the period 1991–2009. Data on the institutional origin of each registration and the number of relevant DNRP registrations were recorded, and systematic patient chart reviews were performed to confirm the diagnosis. Results In total, 110 cases of acromegaly were confirmed, compared with 275 registered cases, yielding a positive predictive value (PPV) of 40%. When restricting the search to the regional highly specialized department of endocrinology, the PPV increased to 53% with no loss of cases with confirmed acromegaly. With a requirement of at least one, two, or three DNRP registrations, the PPV increased, but with a concurrent loss of confirmed cases. Conclusion The DNRP seems to be a useful source for identifying new cases of acromegaly, especially when restricting the search to a relevant regional highly specialized department. The PPV of DNRP data used for this purpose can be increased by including only cases with several registrations. A similar approach may be successfully applied to other rare diseases in which continuity of care is provided by highly specialized departments.

Cancer Incidence in Patients with Acromegaly: A cohort study and meta-analysis of the literature

Context Acromegaly has been associated with increased risk of cancer morbidity and mortality, but research findings remain conflicting and population-based data are scarce. We therefore examined whether patients with acromegaly are at higher risk of cancer. Design A nationwide cohort study (1978 to 2010) including 529 acromegaly cases was performed. Incident cancer diagnoses and mortality were compared with national rates estimating standardized incidence ratios (SIRs). A meta-analysis of cancer SIRs from 23 studies (including the present one) was performed. Results The cohort study identified 81 cases of cancer after exclusion of cases diagnosed within the first year [SIR 1.1; 95% confidence interval (CI), 0.9 to 1.4]. SIRs were 1.4 (95% CI, 0.7 to 2.6) for colorectal cancer, 1.1 (95% CI, 0.5 to 2.1) for breast cancer, and 1.4 (95% CI, 0.6 to 2.6) for prostate cancer. Whereas overall mortality was elevated in acromegaly (SIR 1.3; 95% CI, 1.1 to 1.6), cancer-specific mortality was not. The meta-analysis yielded an SIR of overall cancer of 1.5 (95% CI, 1.2 to 1.8). SIRs were elevated for colorectal cancer, 2.6 (95% CI, 1.7 to 4.0); thyroid cancer, 9.2 (95% CI, 4.2 to 19.9); breast cancer, 1.6 (1.1 to 2.3); gastric cancer, 2.0 (95% CI, 1.4 to 2.9); and urinary tract cancer, 1.5 (95% CI, 1.0 to 2.3). In general, cancer SIR was higher in single-center studies and in studies with <10 cancer cases. Conclusions Cancer incidence rates were slightly elevated in patients with acromegaly in our study, and this finding was supported by the meta-analysis of 23 studies, although it also suggested the presence of selection bias in some earlier studies.

Targeting either GH or IGF-I during somatostatin analogue treatment in patients with acromegaly: A randomized multicentre study

CONTEXT Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. OBJECTIVE To evaluate the effects of targeting either IGF-I or GH during somatostatin analogue (SA) treatment. PATIENTS AND METHODS 84 patients with controlled acromegaly after surgery (n = 23) or SA (n = 61) underwent a GH profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n = 33) or GHnadir (n = 28). SA dose escalation was allowed at baseline and 6 months. MAIN OUTCOME MEASURES GHnadir and IGF-I at baseline and 12 months, and disease-specific Quality of Life (QoL). RESULTS IGF-I and fasting GH levels were comparable between the surgery and the SA group, whereas GHnadir (µg/L) was lower in the surgery group (GHnadir 0.7 ± 0.1 vs 0.3 ± 0.1, P < 0.01). SA dose increase was performed in 20 patients in the GH group and in 8 patients in the IGF-I group (P = 0.02), which increased the number of concordantly controlled patients (P = 0.01). QoL was only mildly affected at baseline in all groups and did not changed consistently during the study. CONCLUSION (1) Discordant values in terms of high GH levels are prevalent in SA patients and more so if applying glucose-suppressed GHnadir; (2) targeting discordant levels of either GH or IGF-I translates into SA dose increase and improved biochemical control; (3) even though QoL was not improved in this study, we suggest biochemical assessment of disease activity to include glucose-suppressed GHnadir also in SA patients.

Evaluation of ICD-10 algorithms to identify hypopituitary patients in the Danish National Patient Registry

Objective Routinely collected health data may be valuable sources for conducting research. This study aimed to evaluate the validity of algorithms detecting hypopituitary patients in the Danish National Patient Registry (DNPR) using medical records as reference standard. Study design and setting Patients with International Classification of Diseases (10th edition [ICD-10]) diagnoses of hypopituitarism, or other diagnoses of pituitary disorders assumed to be associated with an increased risk of hypopituitarism, recorded in the DNPR during 2000–2012 were identified. Medical records were reviewed to confirm or disprove hypopituitarism. Results Hypopituitarism was confirmed in 911 patients. In a candidate population of 1,661, this yielded an overall positive predictive value (PPV) of 54.8% (95% confidence interval [CI]: 52.4–57.3). Using algorithms searching for patients recorded at least one, three or five times with a diagnosis of hypopituitarism (E23.0x) and/or at least once with a diagnosis of postprocedural hypopituitarism (E89.3x), PPVs gradually increased from 73.3% (95% CI: 70.6–75.8) to 83.3% (95% CI: 80.7–85.7). Completeness for the same algorithms, however, decreased from 90.8% (95% CI: 88.7–92.6) to 82.9% (95% CI: 80.3–85.3) respectively. Including data of hormone replacement in the same algorithms PPVs increased from 73.2% (95% CI: 70.6–75.7) to 82.6% (95% CI: 80.1–84.9) and completeness decreased from 94.3% (95% CI: 92.6–95.7) to 89.7% (95% CI: 87.5–91.6) with increasing records of E23.0x. Conclusion The DNPR is a valuable data source to identify hypopituitary patients using a search criteria of at least five records of E23.0x and/or at least one record of E89.3x. Completeness is increased when including hormone replacement data in the algorithm. The consequences of misclassification must, however, always be considered.

Response to “Epidemiology of neuromyelitis optica spectrum disorder’’

1. Patient ascertainment/study design: Data were collected from the period January 1, 2012 to December 31, 2013 retrospectively and prospectively, with screening of medical records starting in December 2012 and ending in May 2015. Patients eligible for study participation were identified based on lists of patients with relevant diagnoses. These lists constitute the background for reports to the different patient registries and thus the same data. Reassessment of each patient confirmed the correct diagnosis and made inclusion of patients with only one core symptom possible. We find that this ensures our patient selection to be as complete as possible.