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1.
Neth J Med ; 74(4): 152-7, 2016 May.
Article in English | MEDLINE | ID: mdl-27185773

ABSTRACT

BACKGROUND: Success rate of thyroid remnant ablation in patients with low-risk differentiated thyroid cancer (DTC) is commonly based on measurement of serum thyroglobulin levels and 185 MBq (5 mCi) diagnostic 131I scanning or neck ultrasound, performed 6-9 months after ablation. In the present study, we report the rates of successful 131I ablation based on a 5550 MBq (150 mCi) post-therapy scan performed 6-9 months after ablation. METHODS: Retrospective cohort study of 77 adult patients with DTC, stage T1-T3, N0 or N1, M0, demonstrating thyroid remnant uptake one week after a 2775 MBq (75 mCi) ablation dose. Six to nine months later, all patients received a 5550 MBq dose of 131I, followed by a post- therapy scan after one week. Complete thyroid ablation was defined as no thyroid remnant uptake and a thyroglobulin level < 0.2 µg/l after thyroid hormone withdrawal. RESULTS: Thyroid ablation was complete in 20 patients (26%). Forty-eight patients (62%) demonstrated persistent remnant uptake. This was associated with thyroglobulin levels > 0.2 µg/l in 24/48, and positive thyroglobulin antibodies in 4/48 patients. CONCLUSION: Thyroid remnant ablation success assessed by 5550 MBq post-therapy scanning was much lower than reported in studies evaluating ablation success based on 185 MBq diagnostic 131I scanning or neck ultrasound. The latter techniques may be too inaccurate to detect thyroid remnants and thus may not be sufficiently reliable to predict long-term disease outcome.


Subject(s)
Carcinoma/radiotherapy , Thyroid Neoplasms/radiotherapy , Ablation Techniques/methods , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma/pathology , Carcinoma/surgery , Female , Humans , Iodine Radioisotopes/administration & dosage , Male , Middle Aged , Neoplasm Staging , Netherlands , Retrospective Studies , Thyroglobulin/blood , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy , Tomography Scanners, X-Ray Computed , Treatment Outcome , Young Adult
2.
Ned Tijdschr Geneeskd ; 152(27): 1497-500, 2008 Jul 05.
Article in Dutch | MEDLINE | ID: mdl-18681356

ABSTRACT

In patients known to have adrenal insufficiency, inadequate adjustment of the glucocorticoid dosage during intercurrent illness can be life threatening. We describe two patients with adrenal insufficiency who died after their glucocorticoid dosage was insufficiently increased during an episode of gastroenteritis and pneumonia, respectively. Another patient died after a few days of fever and vomiting of unknown origin, after a period of refusing her medication. To prevent unnecessary death from Addisonian crisis, we have developed a protocol. Patients with known adrenal insufficiency, as well as their relatives and general practitioners, should repeatedly receive verbal and written instructions on how to deal with physical and severe psychic stress. We teach the patients and their relatives how to use an emergency injection of hydrocortisone, and the patients can consult the on-call endocrinologist by telephone 24 hours a day.


Subject(s)
Addison Disease/drug therapy , Adrenal Insufficiency/drug therapy , Hydrocortisone/therapeutic use , Acute Disease , Adrenal Insufficiency/complications , Adult , Fatal Outcome , Female , Humans , Male , Middle Aged , Risk Factors
3.
Eur J Endocrinol ; 154(5): 675-84, 2006 May.
Article in English | MEDLINE | ID: mdl-16645014

ABSTRACT

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 (< or =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.


Subject(s)
ACTH-Secreting Pituitary Adenoma/surgery , Endoscopy/methods , Pituitary ACTH Hypersecretion/surgery , ACTH-Secreting Pituitary Adenoma/pathology , Adult , Female , Humans , Hydrocortisone/blood , Magnetic Resonance Imaging , Male , Middle Aged , Pituitary ACTH Hypersecretion/pathology , Remission Induction , Retrospective Studies , Sphenoid Bone/surgery , Treatment Outcome
4.
J Neurol Neurosurg Psychiatry ; 75(10): 1489-91, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15377706

ABSTRACT

In 1970 a 20 year old woman presented with a pituitary chromophobe adenoma for which she underwent transfrontal pituitary surgery. In 1978 she had to be reoperated on because of local tumour recurrence, resulting in hypopituitarism. Bromocriptine (5 mg/day) was given for 15 years, but the plasma prolactin levels remained elevated. In 2000 the patient presented with signs and symptoms suggestive of a spinal cord lesion at the mid-thoracic level. A magnetic resonance imaging (MRI) scan showed an extensive leptomeningeal mass extending from the brainstem to L5, with a thoracic syringomyelia at the T7-T8 level. The plasma prolactin level was very high (5114 microg/l). A biopsy showed the presence of a metastasised prolactinoma. On administration of high dose cabergoline, 0.5 mg twice a day orally, the plasma prolactin levels decreased within one month and then normalised within 26 months. Tumour load reduced considerably but unfortunately, her signs and symptoms did not improve. This case illustrates that a high dose dopamine agonist might be an important therapeutic option in patients with a metastasised prolactinoma.


Subject(s)
Antineoplastic Agents/therapeutic use , Brain Stem Neoplasms/secondary , Ergolines/therapeutic use , Hyperprolactinemia/drug therapy , Hyperprolactinemia/etiology , Pituitary Neoplasms/complications , Pituitary Neoplasms/drug therapy , Prolactinoma/complications , Prolactinoma/drug therapy , Adult , Cabergoline , Female , Humans , Magnetic Resonance Imaging , Prolactinoma/pathology , Treatment Outcome
6.
Neth J Med ; 60(1): 29-32, 2002 Mar.
Article in English | MEDLINE | ID: mdl-12074041

ABSTRACT

We report a 25-year-old woman presenting with a flaccid paresis due to severe hypokalaemia as a consequence of distal renal tubular acidosis (dRTA). Six years after presentation of dRTA, she developed overt symptoms of systemic lupus erythematosus (SLE). dRTA in SLE is often secondary to an interstitial nephritis. In contrast to other reports the dRTA did not resolve after treatment with prednisone in our patient. Nephrocalcinosis might be one of the causal factors in the persistence of dRTA.


Subject(s)
Acidosis, Renal Tubular/etiology , Lupus Erythematosus, Systemic/complications , Lupus Nephritis/complications , Paralysis/etiology , Acidosis, Renal Tubular/diagnosis , Adult , Female , Follow-Up Studies , Humans , Kidney Function Tests , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Nephritis/diagnosis , Lupus Nephritis/drug therapy , Muscle Hypotonia , Paralysis/diagnosis , Prednisone/administration & dosage , Risk Assessment , Tomography, X-Ray Computed , Treatment Outcome
7.
Ned Tijdschr Geneeskd ; 146(10): 449-54, 2002 Mar 09.
Article in Dutch | MEDLINE | ID: mdl-11913106

ABSTRACT

Three patients diagnosed with primary hypertension suddenly developed hard-to-treat blood pressure after several years of stable blood pressure. One patient, a man aged 48 years, had developed a renal artery stenosis, which had not been present five years earlier. The other two patients, a man aged 57 years and a woman aged 27 years, were diagnosed with an aldosterone-producing adenoma of the left adrenal gland and a pheochromocytoma, respectively. In patients with previously stable blood pressure, sudden derangement may be due to secondary hypertension on top of the pre-existing primary hypertension. A thorough history and physical examination together with limited laboratory investigations usually leads the way to the correct diagnosis.


Subject(s)
Hypertension/diagnosis , Hypertension/etiology , Adrenal Gland Neoplasms/complications , Adrenal Gland Neoplasms/metabolism , Adrenocortical Adenoma/complications , Adrenocortical Adenoma/metabolism , Adult , Aldosterone/metabolism , Female , Humans , Hyperaldosteronism/complications , Male , Middle Aged , Pheochromocytoma/complications , Renal Artery Obstruction/complications
9.
J Clin Endocrinol Metab ; 86(9): 4161-5, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11549643

ABSTRACT

In GH-deficient adults, rhGH has pronounced effects on total body water, fat free mass, and fat mass. Recently, we observed a gender difference in IGF-I responsivity to rhGH that was sex steroid dependent. The aim of the present study was to assess the effect of rhGH therapy on body composition parameters with due attention to the gender differences in biological responsiveness to rhGH. Forty-four women [36.9 +/- 11.9 yr (mean +/- SD)] and 33 men (37.2 +/- 13.8 yr) with GH deficiency were studied every 6 months during 2 yr. The treatment goal was to achieve IGF-I levels within the age-adjusted normal range. Total body water, fat free mass, and fat mass were measured by bioimpedantiometry. To reach the treatment goal, the daily rhGH dose (IU/kg/d) had to be significantly higher in women than in men at all time intervals. During rhGH therapy, total body water and fat free mass increased significantly in both men and women (P < or = 0.01 by ANOVA), but changes were more pronounced in men. Fat mass decreased during rhGH treatment and reached its nadir at 6 months, which was more pronounced in men than in women (P = 0.02 by ANOVA). After the initial decrease, fat mass increased again and reached baseline values after 2 yr of treatment. In both men and women, the total body water and fat free mass increases were closely related to the IGF-I increments (P < 0.001 by Pearson's correlation test). The decrease in fat mass correlated significantly with the increase in IGF-I in men (r = -0.89, P < 0.001), not in women. Confirming our earlier data, IGF-I responsivity to rhGH was significantly higher in men than in women at all time intervals (P < 0.01 by ANOVA). Total body water and fat free mass responsivities were also higher in men than in women (P < 0.01 by ANOVA). In conclusion, gender differences in IGF-I responsivities to rhGH are accompanied by gender differences in the extent of body composition changes to rhGH. Probably because of these gender differences in IGF-I responsivity, the increases of total body water and fat free mass to rhGH replacement were greater in men than in women. Remarkably, however, in men, only total body water and fat free mass responses relative to changes in IGF-I increased during the 2 yr of rhGH therapy (P = 0.02 and 0.01, respectively, by ANOVA). In our opinion, this phenomenon might be explained by the increasing target organ sensitivity to IGF-I over time.


Subject(s)
Growth Hormone/pharmacology , Human Growth Hormone/deficiency , Adult , Body Composition/drug effects , Body Weight/physiology , Female , Follow-Up Studies , Humans , Insulin-Like Growth Factor I/metabolism , Male , Sex Characteristics
10.
Clin Endocrinol (Oxf) ; 54(1): 45-52, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11167925

ABSTRACT

OBJECTIVE: To analyse the results of different treatment modalities for Nelson's syndrome, which was defined as radiological evidence of a pituitary macroadenoma, fasting plasma ACTH levels of more than 200 pmol/l after stopping glucocorticoid substitution for at least 24 h in a patient who had undergone bilateral adrenalectomy for Cushing's disease. DESIGN: The medical reports of all Nelson's patients known in our hospital were studied with regard to treatment modalities and result of treatment. Clinical remission of Nelson's syndrome was defined as a reduction of tumour size to a diameter of 10 mm or less and fasting plasma ACTH levels less than 200 pmol/l after stopping glucocorticoid substitution for at least 24 h. PATIENTS: Fifteen women with Nelson's syndrome were studied. Bilateral adrenalectomy had been performed 1-29 years before Nelson's syndrome was diagnosed. Before adrenalectomy eight patients had undergone unsuccessful transsphenoidal pituitary surgery. RESULTS: Eight patients were initially followed without surgical or radiotherapeutical intervention during 1-7 years. In seven of them, plasma ACTH levels and tumour volumes increased progressively during this rather short observation period, with development of extrasellar extension in four patients. In one of these patients, who was planned for elective pituitary surgery, massive pituitary haemorrhage occurred which was fatal despite emergency pituitary surgery. Elective pituitary surgery was performed in 11 patients, of whom three were operated twice. Clinical remission was documented in five patients in the first year after operation. In one patient postoperative MR-imaging revealed no residual tumour mass but the postoperative plasma ACTH level was still elevated. In another patient a residual intrasellar macroadenoma and an increased plasma ACTH level remained stable for 22 years. The remaining four patients received postoperative radiotherapy because of residual tumour masses. Of these patients, one had a clinical remission. In two others relatively small residual intrasellar tumour masses remain, with a fasting plasma ACTH level of more than 200 pmol/l in one of them. The fourth patient died of the consequences of progressive tumour growth. Radiotherapy was the only treatment in two patients and did not result in clinical remission. Tumour volumes and plasma ACTH levels at the time of diagnosis of Nelson's syndrome were positively correlated (r = + 0.61, P < 0.05). This correlation was stronger at the moment of decision of either pituitary surgery or radiotherapy (r = + 0.85, P < 0.001). At the end of the follow-up period the correlation between tumour volumes and plasma ACTH levels in the combined pituitary surgery and/or irradiation only group was + 0.77 (P < 0.001). In the pituitary surgery group tumour volumes before and after surgery were directly correlated (r = + 0.70, P < 0.05). CONCLUSIONS: Our results demonstrate that pituitary surgery of Nelson's macroadenomas is more successful when Nelson's adenomas are relatively small. Pituitary surgery should be performed before extrasellar expansion of the tumour occurs in order to attain long lasting remissions. Pituitary irradiation should be performed postoperatively in all patients with residual tumour. Our data also illustrate that in patients with Nelson's syndrome, plasma ACTH levels can reliably be used as an indirect approximation for tumour volume.


Subject(s)
Nelson Syndrome/surgery , Adrenalectomy , Adrenocorticotropic Hormone/blood , Adult , Combined Modality Therapy , Cushing Syndrome/surgery , Female , Follow-Up Studies , Humans , Middle Aged , Nelson Syndrome/diagnosis , Nelson Syndrome/diagnostic imaging , Radiography , Treatment Outcome
11.
Ned Tijdschr Geneeskd ; 144(47): 2264-8, 2000 Nov 18.
Article in Dutch | MEDLINE | ID: mdl-11109472

ABSTRACT

OBJECTIVE: Evaluation of clinical presentation, treatment and follow-up of patients with intracranial germinoma in the Netherlands. DESIGN: Retrospective. METHOD: The case histories of 32 patients with histologically verified intracranial germinoma, registered in the period 1983-1999 in the Pathological Anatomical Nationwide Automated Archive (PALGA), were studied. Fifty of the 59 registered patients were found of whom 6 had no germinoma. Informed consent was obtained from 32 of the 44 patients with respect to studying their medical records for age, symptoms at presentation, diagnostic investigations, presence of tumour markers, treatment and follow up. RESULTS: The patient group consisted of 23 men and 9 women aged 6 to 35.6 years (mean: 17.3) and was subdivided with respect to their tumour localization. In patients with pineal localization symptoms of increased intracranial pressure and eye movement disorders were most prominent, whereas in patients with suprasellar localization endocrine disorders prevailed. Thirty-one patients were treated with radiotherapy, one with combined radiotherapy and chemotherapy and one surgically. Twenty-six patients had remained disease free after a median follow-up of 39 months (range: 0-144 months). One patient developed an intracranial embryonal carcinoma and another a testis seminoma. Two patients died because of recurrences. Two other patients died of causes not directly related to the germinoma. CONCLUSION: At the time of this study 84% of all patients treated with radiotherapy were disease-free. Although the percentage patients who had recovered after treatment (surgical and radiotherapy) was high, many patients either already had or subsequently developed neurological and endocrinological deficiencies.


Subject(s)
Brain Neoplasms/diagnosis , Brain Neoplasms/therapy , Germinoma/diagnosis , Germinoma/therapy , Adolescent , Adult , Brain Neoplasms/complications , Brain Neoplasms/physiopathology , Cause of Death , Child , Diagnosis, Differential , Disease-Free Survival , Endocrine System Diseases/etiology , Female , Germinoma/complications , Germinoma/physiopathology , Humans , Intracranial Hypertension/etiology , Male , Neoplasms, Germ Cell and Embryonal/etiology , Netherlands , Ocular Motility Disorders/etiology , Recurrence , Registries , Retrospective Studies , Treatment Outcome
13.
J Nucl Med ; 41(4): 643-6, 2000 Apr.
Article in English | MEDLINE | ID: mdl-10768565

ABSTRACT

UNLABELLED: For differentiated, nonmedullary thyroid carcinoma, postsurgical ablation of thyroid remnants and treatment of residual tumor and metastases with 131I is a potentially curative therapy. The aim of this study was to optimize the diagnostic protocol for the follow-up of thyroidectomized patients. METHODS: Two hundred fifty-four patients (187 females, 67 males; mean age, 45 y; range, 8-83 y) were studied retrospectively for a mean follow-up period of 2.7 y (range, 1-12.5 y). An evaluation study consisted of a low-dose 131I diagnostic procedure under hyperthyroid conditions (thyroid-stimulating hormone > 30 MicroU/mL), 201TI scintigraphy, and measurement of thyroglobulin (Tg) under hypothyroid conditions. A total of 254 preablation studies (1 study per patient) and 586 follow-up studies (average number of studies, 2.3 per patient) were evaluated. RESULTS: Before ablation, low-dose 131I screening was useful to estimate the size of the thyroid remnant. Low Tg levels (<10 pmol/L) indicated the absence of metastases. After ablation, undetectable Tg levels indicated the absence of tumor recurrence. When Tg levels were high (>10 pmol/L), local recurrence or metastases were always observed, providing the basis for additional high-dose 131I therapy. In these patients, 201TI imaging did not provide a significant contribution to patient management. In the case of autoantibodies against Tg, both low-dose 131I screening and 201TI scintigraphy may be advocated to allow an aggressive diagnostic work-up. CONCLUSION: Tg plays a key role in follow-up and in making decisions to treat patients with differentiated thyroid carcinoma. The role of 201TI imaging is very limited. In patients with negative low-dose 131I screening, 201TI scintigraphy can be considered when Tg is elevated or cannot be evaluated because of autoantibodies against Tg. Under such circumstances, administration of a therapeutic 131I dose without 201TI imaging can be considered.


Subject(s)
Adenocarcinoma, Follicular/diagnostic imaging , Adenocarcinoma, Follicular/radiotherapy , Carcinoma, Papillary/diagnostic imaging , Carcinoma, Papillary/radiotherapy , Iodine Radioisotopes/therapeutic use , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/radiotherapy , Adenocarcinoma, Follicular/blood , Carcinoma, Papillary/blood , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Care , Radionuclide Imaging , Radiopharmaceuticals , Thallium Radioisotopes , Thyroglobulin/blood , Thyroid Neoplasms/blood , Thyroidectomy
14.
J Clin Endocrinol Metab ; 85(3): 1121-5, 2000 Mar.
Article in English | MEDLINE | ID: mdl-10720049

ABSTRACT

GH production in healthy women is about thrice that in men. Yet insulin-like growth factor I (IGF-I) levels are similar, suggesting a lower responsivity to GH in women. In untreated GH-deficient adults, basal IGF-I levels are reportedly lower in females than in males, and the therapeutic recombinant human GH (rhGH) dose required to achieve optimal IGF-I levels is higher in the former, suggesting a pivotal role of estrogens on rhGH requirement in GH-deficient patients. We, therefore, analyzed our 2-yr data on the effect of rhGH on serum IGF-I in 77 GH-deficient patients (33 men, mean +/- SD age, 37.2 +/- 13.8 yr; 44 women, mean +/- SD age, 36.9 +/- 11.9 yr) with due attention to gender differences and to the effects of sex hormone replacement. Of the 44 women, 33 had estrogen substitution. Of the 33 men, 23 were on androgen replacement. Patients (11 premenopausal women and 10 men) not on hormonal replacement were eugonadal. Basal IGF-I levels in untreated GH-deficient women were significantly lower than in men (8.8 +/- 0.7 nmol/L vs. 12.2 +/- 0.9 nmol/L; P < 0.01), despite similar basal GH levels. The daily rhGH dose per kg body weight required to normalize IGF-I in women was higher than in men, the difference being statistically significant at all time points (P < 0.05-0.01). The IGF-I increase (delta) per IU GH/day x kg over the 24-month period was about twice higher in men than in women. Also calculated on a weight basis, rhGH responsivity (rhGH responsivity = (deltaIGF1(nmol/L)/dose (IU/day/kg)) was higher in men than in women at all time intervals (P < 0.05-0.01). Estrogen replacement in women significantly increased rhGH requirement. The rhGH dose per kg body weight required in estrogen-substituted women was significantly higher than in nonestrogen-substituted women (P < 0.01 at t = 18 and 24 months, respectively). In women on estrogen substitution, rhGH responsivity plateaued from 6 months on, whereas in eugonadal women without estrogen substitution the responsivity for rhGH increased over time. In men, the reverse was true; rhGH responsivity increased over time in men on androgen substitution, but plateaued in men without androgen substitution. The mechanisms underlying this gender difference are not known. Differential influences of estrogens and androgens on the expression of the GH receptor gene and IGF-I messenger RNA may be operative. The present study confirms short-term data published in the literature on a sex difference in rhGH dose requirement in GH-deficient patients. It furthers extends the data by demonstrating that this sex difference in GH responsivity persists and changes during the 24 months of the study. Moreover, it shows that estrogen replacement blunts the IGF-I response to rhGH in women, whereas in men with androgen substitution the responsivity increases over time, thus bearing a risk of undertreatment in women and overtreatment in men.


Subject(s)
Gonadal Steroid Hormones/therapeutic use , Growth Hormone/therapeutic use , Hormone Replacement Therapy , Human Growth Hormone/deficiency , Insulin-Like Growth Factor I/metabolism , Adult , Androgens/therapeutic use , Cohort Studies , Estrogen Replacement Therapy , Female , Growth Hormone/blood , Human Growth Hormone/blood , Humans , Male , Sex Characteristics , Time Factors
15.
J Clin Endocrinol Metab ; 84(11): 3991-9, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10566639

ABSTRACT

In 14 women, aged 47.2 +/- 10.5 yr, bilaterally adrenalectomized for Cushing's disease 13.6 +/- 7.7 yr before, all receiving conventional doses of glucocorticoid and mineralocorticoid substitution, body composition was studied with regard to body fat, body fat distribution, fat-free mass, and bone mineral density. The data were compared with those of 14 healthy women of similar age, body mass index, and menopausal state. Five different body composition measurement methods were compared, i.e. body densitometry by underwater weighing (UWW), total body water measurement by deuterium dilution (D2O dilution), dual energy x-ray absorptiometry (DXA), bioelectrical impedance spectrometry (BIS), and skinfold measurements, using a four-component model (4C-model) as the reference method. In the patients the percent body fat was significantly higher than that in the controls as determined by all methods, whereas fat-free mass was significantly lower when measured with the 4C-model, UWW, D2O dilution, DXA, or BIS. Measured by DXA, the percent trunk fat, estimated as [fat mass of the trunk (g)/total fat mass (g)] x 100%, was significantly higher in the patients than in the controls (39.3 +/- 6.4% and 29.9 +/- 7.8%, respectively; P < 0.001). Measured by DXA, there was no difference in total bone mineral density between the groups. Differences between the 4C-model, UWW, D2O dilution, and DXA for determination of percent body fat were rather small. Skinfold measurements and BIS results, however, deviated substantially from those obtained using the 4C-model. The study indicates that adrenalectomized patients receiving conventional glucocorticoid substitution have increased body fat percentages with a centripetal fat distribution and lowered fat-free mass, but normal bone mineral density. Furthermore, the study indicates that for clinical practice, DXA, D2O dilution, UWW, and the 4C-model can be used for determination of body composition in this patient group, whereas the more convenient bedside methods, BIS and skinfold measurements, did not give reliable results. We suppose that glucocorticoid overreplacement in adrenalectomized patients might be the cause of their abnormal body composition, although GH deficiency after pituitary surgery could have played a contributory role in some of the patients.


Subject(s)
Adrenalectomy , Body Composition , Cushing Syndrome/surgery , Absorptiometry, Photon , Adipose Tissue , Adult , Body Water , Body Weight , Bone Density , Deuterium , Electric Impedance , Female , Glucocorticoids/therapeutic use , Humans , Immersion , Indicator Dilution Techniques , Middle Aged , Mineralocorticoids/therapeutic use , Skinfold Thickness
16.
J Endocrinol Invest ; 22(6): 446-50, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10435854

ABSTRACT

Diagnosing growth hormone deficiency in adults is difficult. Provocation tests are most commonly used for the diagnosis with the insulin-induced hypoglycemia test nowadays considered as the "gold standard". The role of IGF-I concentrations in diagnosing growth hormone deficiency in adults is under discussion. In 58 adult patients with proven growth hormone deficiency, the sensitivity and specificity of IGF-I concentrations in relation to growth hormone deficiency were evaluated. Reference values of plasma IGF-I were obtained from 53 healthy volunteers. Using a calculated cut-off concentration of 15 nmol/l we were able to demonstrate that IGF-I concentration is a reliable screening method for growth hormone deficiency. Using this cut-off point in a patient population younger than 40 years of age, sensitivity was 90% and specificity 89%. For patients exceeding the age of 40 years, sensitivity, specificity and positive predictive value were rather low, but the negative predictive value was as high as 90%, indicating that for patients over 40 years IGF-I concentrations above 15 nmol/l exclude growth hormone deficiency. In summary, under the age of 40 years measuring plasma IGF-I provides an useful tool to diagnose growth hormone deficiency, whereas above 40 plasma IGF-I values exceeding 15 nmol/l virtually exclude growth hormone deficiency.


Subject(s)
Human Growth Hormone/deficiency , Insulin-Like Growth Factor I/metabolism , Adult , Aged , Aging/metabolism , Biomarkers , Body Mass Index , Female , Humans , Male , Middle Aged , Radioimmunoassay , Reference Values
17.
J Endocrinol Invest ; 22(1): 70-5, 1999 Jan.
Article in English | MEDLINE | ID: mdl-10090141

ABSTRACT

A 25-year-old woman developed Nelson's syndrome, 3 years after successful bilateral adrenalectomy for Cushing's disease. Despite pituitary surgery and radiotherapy the tumour showed invasive growth, leading to visual disturbance, paresis of the oculomotor nerve and, 34 years after adrenalectomy, to death by widespread purulent leptomeningitis. Autopsy revealed a large adenohypophyseal carcinoma with a metastasis attached to the dura, both tumours showing immunocytochemical staining for ACTH and TSH. We review the literature on metastatic adenohypophyseal carcinoma in Cushing's disease and Nelson's syndrome and discuss the role of proliferation markers as indicators of malignant progression.


Subject(s)
Carcinoma/pathology , Nelson Syndrome/pathology , Pituitary Neoplasms/pathology , Adrenalectomy , Adrenocorticotropic Hormone/analysis , Adult , Carcinoma/chemistry , Cell Transformation, Neoplastic , Cushing Syndrome/complications , Cushing Syndrome/surgery , Fatal Outcome , Female , Humans , Neoplasm Invasiveness , Neoplasm Metastasis , Pituitary Neoplasms/chemistry , Thyrotropin/analysis
18.
Neth J Med ; 52(3): 111-5, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9599968

ABSTRACT

BACKGROUND: Autonomous (hyper-)secretion of cortisol without classical stigmata of Cushing's syndrome occurs in 10-15% of patients with incidentally detected adrenal tumors (incidentalomas). METHODS: We present the clinical and biochemical data of four such patients. Two patients had hypertension and one both hypertension and non-insulin-dependent diabetes mellitus, but none showed classical stigmata of Cushing's syndrome. RESULTS: All patients showed insufficient suppression of plasma cortisol during a 1 mg dexamethasone screening test. Plasma ACTH levels were suppressed in all patients. However, in three out of four patients the diurnal rhythm of plasma cortisol was intact and these three patients also showed a response of plasma cortisol after administration of corticotropin-releasing hormone. All patients underwent unilateral adrenalectomy. A carcinoma was found in one patient and an adenoma in the remaining three. Postoperatively, blood pressure had normalized in 2 out of 3 hypertensive patients, whereas non-insulin-dependent diabetes mellitus had disappeared in 1 patient. Postoperative endocrine evaluation showed no abnormalities anymore. CONCLUSIONS: We conclude that dexamethasone testing may reveal autonomous (hyper-)secretion of cortisol in adrenal incidentalomas. Adrenalectomy should be considered, especially when hypertension and/or non-insulin-dependent diabetes mellitus are present. One should be alert to the development of adrenal insufficiency after unilateral adrenalectomy.


Subject(s)
Adrenal Gland Neoplasms/complications , Cushing Syndrome/etiology , Adrenal Gland Neoplasms/surgery , Adrenocorticotropic Hormone/blood , Aged , Cushing Syndrome/diagnosis , Dexamethasone , Female , Humans , Hydrocortisone/blood , Male , Middle Aged , Radioimmunoassay
19.
Clin Immunol Immunopathol ; 78(1): 90-2, 1996 Jan.
Article in English | MEDLINE | ID: mdl-8599891

ABSTRACT

Snell-Bagg mice and Ames dwarf mice repeatedly show severe immunodeficiencies, affecting mostly the thymus- dependent lymphocyte system, probably caused by growth hormone deficiency. In growth hormone-deficient children contradictory data on the immune status have been reported. We investigated indices of cellular immunity in 22 adult patients with proven growth hormone deficiency in comparison to those in 100 health volunteers. Cellular immunity was assessed using total leukocyte count, percentage lymphocytes, and percentage and absolute numbers of CD3, CD4, CD8, CD19, and CD3-CD56+ (NK)-cells. Comparison revealed statistically significantly lower percentage and absolute number of NK-cells (P < 0.001). Except for a trend toward an increased CD4/CD8 ratio, no statistically significant differences for B- and T-lymphocytes could be observed. No correlation between the percentage and absolute number of NK-cells, on one hand, and the duration of growth hormone deficiency or prolactin level, on the other hand, could be demonstrated. In all these respects men did not differ from women. So, in growth hormone-deficient adults the percentage and absolute number of NK-cells are decreased.


Subject(s)
Growth Hormone/deficiency , Killer Cells, Natural/pathology , Lymphopenia/immunology , Adolescent , Adult , Aged , Female , Humans , Immunity, Cellular , Lymphocyte Count , Lymphopenia/etiology , Male , Middle Aged
20.
J Hypertens ; 13(12 Pt 2): 1585-8, 1995 Dec.
Article in English | MEDLINE | ID: mdl-8903614

ABSTRACT

BACKGROUND: Circadian changes in blood pressure are paralleled by analogous circadian changes in plasma catecholamines: blood pressure, plasma noradrenaline and adrenaline fall at night. OBJECTIVE: To determine whether adrenaline is a prerequisite for the nocturnal fall in blood pressure, the circadian blood pressure profile was studied in adrenalectomized subjects, lacking circulating adrenaline. SUBJECTS AND METHODS: Ten adrenalectomized subjects and 10 healthy age-matched normotensive controls underwent 24-h non-invasive ambulatory blood pressure monitoring with the Oxford Medilog device. Measurements were taken every 15 min from 7.00 a.m. until 11.59 p.m and every 30 min from 12 midnight until 6.59 a.m. The nocturnal blood pressure fall was calculated for each subject. RESULTS: Mean +/- SD systolic blood pressure decreased at night by 13.2 +/- 9.5 mmHg in the adrenalectomized and by 11.7 +/- 7.3 mmHg (NS) in the control subjects. There was no significant difference between groups in the nocturnal diastolic blood pressure fall (14.4 +/- 5.1 and 13.1 +/- 5.2 mmHg, respectively). Systolic blood pressure decreased by > 10 mmHg in five of the adrenalectomized and eight of the control subjects. Diastolic blood pressure decreased by > 10 mmHg in eight of the adrenalectomized and eight of the control subjects. CONCLUSION: The normal nocturnal fall in blood pressure in adrenalectomized subjects indicates that circulating adrenaline is not required for a normal circadian blood pressure rhythm.


Subject(s)
Blood Pressure Monitoring, Ambulatory , Circadian Rhythm/physiology , Epinephrine/blood , Norepinephrine/blood , Adrenalectomy , Adult , Female , Humans , Male
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