Search Results

You are looking at 1 - 10 of 17 items for

  • Author: A R Hermus x
Clear All Modify Search
Full access

Peter A. van Liessum, Gerlach F. Pieters, Anthony G. Smals, Ad R. Hermus, TheoJ. Benraad and Peter W. Kloppenborg

Abstract.

The recommended dosage schedules for intermittent sc therapy with the somatostatin analogue octreotide in acromegaly vary widely, from 100 to 1500 μg daily. As acute administration of octreotide has been shown to predict its long-term response, we performed a single-dose response study in 5 patients with active acromegaly using doses of 25, 50, 100, 200 and 400 μg octreotide as well as a placebo injection. Plasma GH of 2 patients did not normalize after any of the injections, but nadir plasma GH overall gradually decreased as doses were increased from 25 to 400 μg. The 400 μg octreotide dose was superior with regard to the duration of plasma GH suppression to below 5 μg/l or 25% of the basal GH level, the mean GH as a percentage of the basal level over the first 4 and 8 h, and the integrated reduction of plasma GH during the first 4 and 8 h. The postprandial integrated insulin secretion during the first 3 h after injection of the octapeptide was significantly lower after 50, 100 and 400 μg than after the placebo injection. The mean plasma glucose as a percentage of the basal level during the first 8 h was significantly higher after octreotide after the 200 and 400 μg injections. Minor adverse events were seen in 2 patients after injection of 200 and 400 μg octreotide. Within the limitations of this single-dose response study it was concluded that injection of 400 μg octreotide yields the best results with regard to suppression of GH secretion, whereas the 50, 100 and 200 μg doses are superior to 25 μg, but do not differ from each other.

Full access

M A E M Wagenmakers, R T Netea-Maier, J B Prins, T Dekkers, M den Heijer and A R M M Hermus

Objective

The determinants that cause impaired quality of life (QOL) in patients in long-term remission of Cushing's syndrome (CS) are unknown. The aim of this study was to get more insight into the patient and disease characteristics related to impaired QOL in these patients.

Design

Cross-sectional study.

Methods

The QOL of 123 patients in remission of CS (age 52.2±12.0 years, 106 women, duration of remission 13.3±10.4 years, 80% pituitary CS), assessed with seven validated questionnaires, was compared with the QOL of an age- and sex-matched control group (n=105). To investigate the influence of the aetiology of CS on QOL, patients in remission of pituitary and adrenal CS were compared. Furthermore, the influence of hormonal deficiencies, treatment strategy, duration of remission, gender and age on QOL was investigated.

Results

QOL in the total patient group and each patient subgroup was significantly worse on practically all dimensions of questionnaires compared with the control group (P<0.05), except for patients in remission of pituitary CS without hormonal deficiencies who had an impaired QOL on 50% of the QOL dimensions. Subgroup analysis revealed no difference in QOL between different patient groups, especially no difference between patients in remission of adrenal and pituitary CS. Female gender and a shorter duration of remission had a negative influence on QOL in the patient group.

Conclusions

QOL remains impaired in patients in long-term remission of CS regardless of aetiology, presence of hormonal deficiencies and treatment strategies. More research is needed to establish the causes.

Full access

A. E. M. Smals, G. F. F. M. Pieters, A. G. H. Smals, A. R. M. M. Hermus, Th. J. Benraad and P. W. C. Kloppenborg

Abstract. In acromegalics, the percent peak GH responses to TRH (pTRH) and bromocriptine (pBr) are inversely related with those to GHRH, favouring the hypothesis that in the adenomas of some patients there is a preponderance of GH-producing cells with lactotrope-like characteristics, whereas in others pure somatotropes predominate. The aim of the present study was to investigate whether patients responsive to TRH with allegedly lactotrope-like tumours differ from those patients not responding to TRH with more somatotrope-like adenomas in their answer to the GH inhibitors Br and SRIH and the releasing hormones GHRH and GnRH. The present study demonstrates that the observed reciprocal relations between the GH responses to GHRH, TRH and Br are only present in acromegalics paradoxically responding to TRH (pGHRH vs pTRH −0.73, pGHRH vs pBr −0.60, pTRH vs pBr +0.54, P < 0.0002–P < 0.02, N = 20), not in TRH-non-responders (N = 10). In contrast, in these latter patients, not in the former, close relations were found between the percent peak GH responses to GnRH (pGnRH) and pGHRH (r = +0.81, P < 0.005) and between pGnRH and the percent maximum GH decrements in response to SRIH (pSRIH) (r = +0.64, P < 0.05). Expectedly, the GH response to Br in the TRH-responders was significantly higher than in the non-responders (75 ± 4% vs 54 ± 3%, P < 0.02), although it was also substantial in the latter. The GH response to SRIH was remarkedly similar in both groups (64 ± 5 vs 57 ± 9%, P > 0.10). Although the close relations between the GH responses to releasing and inhibiting agents favour the presence of GH-secreting tumours with more somatotrope or more lactotrope characteristics in subsets of acromegalics, they do not effectively predict the therapeutic response to these suppressive agents.

Full access

Ad R Hermus, Gerlach F Pieters, George F Borm, Albert A Verhofstad, Anthony G Smals, Theo J Benraad and Peter W Kloppenborg

A 70-year-old man with mild signs and symptoms of Cushing's syndrome due to an ACTH-secreting pituitary adenoma is described. He had a completely unpredictable pattern of urinary excretion of cortisol; 24 h urine for determination of cortisol excretion was collected daily at home on 725 consecutive days. During this period there were eight episodes in which urinary cortisol excretion exceeded the upper limit of normal. Within these episodes the pattern of cortisol secretion was extremely unpredictable, with cortisol excretion ranging from normal to highly elevated. Using a Cluster Analysis Program 61 pulses of cortisol excretion were detected within the eight periods of cortisol hypersecretion. The interval between two pulses varied from 2 to 12 days. Between the periods of cortisol hypersecretion, urinary cortisol excretion was completely normal, lasting from 4 to 102 days. There was no difference in the clinical expression of Cushing's syndrome between the periods of elevated and normal urinary cortisol excretion. During the last 439 days of the observation, cortisol was also measured in saliva collected at home at 09.00 after an overnight fast. The salivary cortisol pattern closely resembled that of urinary cortisol excretion and there was a significant correlation between salivary cortisol levels and 24 h urinary cortisol excretion in the 24 h after (r=0.42, p<0.0001, Spearman) and before saliva collection (r = 0.44, p<0.0001). On 71% of occasions cortisol peaks in saliva, as detected by the Cluster Analysis Program, coincided with urinary cortisol peaks. We conclude that daily measurement of cortisol in saliva, collected at home, is a convenient and reliable method for detecting intermittent hypercortisolism in patients with Cushing's syndrome.

Full access

Hedi L Claahsen-van der Grinten, Kristof Duthoi, Barto J Otten, Frank C H d'Ancona, Christina A Hulsbergen-vd Kaa and Ad R M M Hermus

Background

In contrast to the high incidence of testicular adrenal rest tumours (TART) in adult male patients with congenital adrenal hyperplasia (CAH), ovarian adrenal rest tumours in female CAH patients are very rare and other locations of adrenal rest tumours have never been reported. Here, we report on an adult patient with CAH due to 3β-hydroxysteroid dehydrogenase (HSD) deficiency with bilateral TART and additionally a large perirenal adrenal rest tumour.

Case report

The patient was known with CAH due to 3β-HSD deficiency and treated with hydrocortisone and fludrocortisone since the neonatal period. In puberty, there was lack of compliance with consequently high POMC concentrations. At the age of 16 years, bilateral TART were detected by scrotal ultrasound. Intensifying glucocorticoid medication did not result in decrease in POMC concentrations and shrinkage of size of the tumours. At the age of 23 years, abdominal ultrasound was performed because of abdominal complaints, showing a round inhomogeneous structure with a diameter of 4 cm near the left renal hilus. A computer tomography scan showed a multinodular lesion in the retroperitoneal region beside the left kidney. Histological investigation after removal of the tumour showed sheets of large polygonal cells with abundant eosinophilic cytoplasm, separated by dense fibrous tissue strands. The histological and immunohistochemical profile resulted in a diagnosis of an adrenal rest tumour.

Conclusion

In adult CAH patients, ectopic adrenal rest tumours can be present outside the testicular region. Further investigations are necessary to determine whether regularly screening for these tumours is useful.

Full access

R T Netea-Maier, E J van Lindert, M den Heijer, A van der Eerden, G F F M Pieters, C G J Sweep, J A Grotenhuis and A R M M Hermus

Objective and design: The endoscopic technique has been recently introduced in the field of transsphenoidal pituitary surgery. This technique allows inspection of sellar, supra- and parasellar structures and removal of the tumor under direct visualization, is minimally traumatic and permits easier reoperations. This is the first report on the results of endoscopic surgery for patients with Cushing’s disease. Our aim was to retrospectively analyze the results of pituitary surgery in 35 consecutive patients with Cushing’s disease operated in our hospital after the introduction of the endoscopic technique (1998–2004).

Methods: Remission was defined as suppression of plasma cortisol (≤50 nmol/L) after 1 mg dexamethasone overnight determined in the first 3 months after surgery and disappearance of clinical signs and symptoms of hypercortisolism. The patients were followed for an average of 27 months (range 4 to 81 months, median 20 months).

Results: Pituitary MRI showed a macroadenoma in 6 patients, a microadenoma in 17 patients and no adenoma in 12 patients. After the initial surgery 27 patients (77%) were in remission. None of the patients had a relapse during follow-up. In the remaining 8 patients hypercortisolemia persisted after surgery. Three of them had a second endoscopic pituitary surgery resulting in remission in two patients. In one patient a second endoscopic pituitary surgery will soon follow. The remaining four patients were treated with radiotherapy postoperatively. Two of them were at the time of data collection in remission. One patient from the remission group had a serious epistaxis and three patients had cerebrospinal fluid leakage, one requiring an external lumbar drain, shortly after surgery. No complications were recorded in the failure group. Postoperatively 34% of all patients required substitution with levothyroxine, 40% required substitution with glucocorticoids, 17% received estrogens or testosterone and 6% still required desmopressin.

Conclusions: Endoscopic transsphenoidal pituitary surgery resulted in our series of patients with Cushings disease in an excellent postoperative remission rate. A randomized clinical trial, comparing endoscopic and conventional pituitary surgery in patients with Cushings disease, is needed to determine the pros and cons of both techniques.

Full access

Cornelie D Andela, Han Repping-Wuts, Nike M M L Stikkelbroeck, Mathilde C Pronk, Jitske Tiemensma, Ad R Hermus, Adrian A Kaptein, Alberto M Pereira, Noelle G A Kamminga and Nienke R Biermasz

Context

Patients with pituitary disease report impairments in Quality of Life (QoL) despite optimal biomedical care. Until now, the effects of a self-management intervention (SMI) addressing psychological and social issues for these patients and their partners have not been studied.

Objective

To examine the effects of a SMI i.e. Patient and Partner Education Programme for Pituitary disease (PPEP-Pituitary).

Design and subjects

A multicentre randomized controlled trial included 174 patients with pituitary disease, and 63 partners were allocated to either PPEP-Pituitary or a control group. PPEP-Pituitary included eight weekly sessions (90 min). Self-efficacy, bother and needs for support, illness perceptions, coping and QoL were assessed before the intervention (T0), directly after (T1) and after six months (T2). Mood was assessed before and after each session.

Results

Patients in PPEP-Pituitary reported improved mood after each session (except for session 1). In partners, mood only improved after the last three sessions. Patients reported higher self-efficacy at T1 (P = 0.016) which persisted up to T2 (P = 0.033), and less bother by mood problems directly after PPEP-Pituitary (P = 0.01), but more bother after six months (P = 0.001), although this increase was not different from baseline (P = 0.346). Partners in PPEP-Pituitary reported more vitality (P = 0.008) which persisted up to T2 (P = 0.034). At T2, partners also reported less anxiety and depressive symptoms (P ≤ 0.014).

Conclusion

This first study evaluating the effects of a SMI targeting psychosocial issues in patients with pituitary disease and their partners demonstrated promising positive results. Future research should focus on the refinement and implementation of this SMI into clinical practice.

Full access

Mark R Postma, Romana T Netea-Maier, Gerrit van den Berg, Jens Homan, Wim J Sluiter, Margreet A Wagenmakers, Alfons C M van den Bergh, Bruce H R Wolffenbuttel, Ad R M M Hermus and André P van Beek

Objective

To assess the influence of long-acting somatostatin analogs (SSTA) after initial pituitary surgery on long-term health-related quality of life (HR-QoL) in relation to disease control in patients with acromegaly.

Design

This is a cross-sectional study in two tertiary referral centers in The Netherlands.

Patients and methods

One hundred and eight patients with acromegaly, in whom transsphenoidal (n=101, 94%) or transcranial (n=7, 6%) surgery was performed. Subsequently, 46 (43%) received additional radiotherapy and 41 (38%) were on postoperative treatment with SSTA because of persistent or recurrent disease at the time of study. All subjects filled in standardized questionnaires measuring HR-QoL. Disease control at the time of study was assessed by local IGF1 SDS.

Results

IGF1 SDS were slightly higher in patients treated with SSTA in comparison with patients without use of SSTA (0.85±1.52 vs 0.25±1.21, P=0.026), but the percentage of patients with insufficient control (IGF1 SDS >2) was not different (17 vs 9%, P=0.208). Patients using SSTA reported poorer scores on most subscales of the RAND-36 and the acromegaly QoL and on all subscales of the multidimensional fatigue inventory-20. A subgroup analysis in patients with similar IGF1 levels (SSTA+, n=26, IGF1 SDS 0.44±0.72 vs SSTA−, n=44, IGF1 SDS 0.41±0.65) revealed worse scores on physical functioning, physical fatigue, reduced activity, vitality, and general health perception across all HR-QoL questionnaires in patients treated with SSTA.

Conclusion

QoL is impaired in association with the need for prolonged postoperative therapy by SSTA in patients with acromegaly despite similar IGF1 levels.

Full access

H A van Duyvenvoorde, M J E Kempers, Th B Twickler, J van Doorn, W J Gerver, C Noordam, M Losekoot, M Karperien, J M Wit and A R M M Hermus

Context

Acid-labile subunit (ALS) deficiency due to homozygous inactivation of the ALS gene (IGFALS) is associated with moderate short stature, and in few cases pubertal delay. The clinical expression of heterozygosity is unknown.

Objective

To investigate the clinical, laboratory, and radiological features of homozygous and heterozygous carriers of a novel mutation in the ALS gene in comparison with non-carriers.

Subjects

Three short Kurdish brothers and their relatives.

Results

The index cases presented with short stature, microcephaly, and low circulating IGF-I and IGF-binding protein-3 (IGFBP-3), and undetectable ALS levels. Two were known with a low bone mineral density and one of them had suffered from two fractures. We found a novel homozygous ALS gene mutation resulting in a premature stop codon (c.1490dupT, p.Leu497PhefsX40). The IGF-I, IGFBP-3, and ALS 150 kDa ternary complex was absent, and ALS proteins in serum were not detected with western blot. IGFPB-1 and IGFPB-2 were low and there was a mild insulin resistance. Five heterozygous carriers tended to have a lower height and head circumference than five non-carriers, and had low plasma ALS and IGFBP-3 levels. Bone mineral (apparent) density was low in two out of three homozygous carriers, and also in four out of nine relatives.

Conclusions

The clinical presentation of homozygous ALS mutations may, besides short stature, include microcephaly. Heterozygous carriers may have less statural and head growth, suggestive for a gene dosage effect.

Full access

Annenienke C van de Ven, Romana T Netea-Maier, Femmie de Vegt, H Alec Ross, Fred C G J Sweep, Lambertus A Kiemeney, Johannes W Smit, Ad R Hermus and Martin den Heijer

Objective

The aim of this study was to investigate the influence of age on the association between thyroid function and mortality.

Design

The Nijmegen Biomedical Study is a population-based study, comprising 5816 randomly selected adults of all age groups without previously known thyroid disease.

Methods

TSH, free thyroxine (FT4) and peroxidase antibodies were measured in 2002–2003. The number of deaths were established in 2012 (median follow-up time 9.4 years).

Results

Subclinical thyrotoxicosis was associated with mortality in subjects aged <65 years (hazard ratio (HR) 2.5, 95% CI 1.1–5.7), but not in subjects aged >65 years. As for thyroid function within the normal range: in the 493 participants aged 80 years or older, an FT4 level in the high-normal range (18.5–22 pmol/l) was associated with a higher mortality in comparison with FT4 levels in the middle range (11.5–15.0 pmol/l): HR 1.7 (95% CI 1.0–2.9). In these elderly, TSH levels within the high-normal range (3.0–4.0 mIU/l) were also associated with a higher mortality in comparison with TSH levels within the middle range (1.0–2.0 mIU/l): HR 1.8 (95% CI 1.0–3.1).

Conclusions

The relationship between thyroid function and mortality differs according to age. This finding might (partially) explain the discrepant results of previous studies examining the relationship between thyroid function and mortality in different age groups.