Biomedical subjects

G van den Berg

Publications and source records attributed to G van den Berg.

At least 19 recordsLinked to original sources

PubMed2006

[Long-term follow-up is indicated after surgery for a phaeochromocytoma].

Two patients presented with symptoms that suggested a recurrence of phaeochromocytoma, 17 and 14 years after a first manifestation of this disease for which they had undergone successful surgery. The first patient, a 57-year-old man, had typical symptoms of phaeochromocytoma and had recently experienced deterioration of the glycaemic control of his diabetes mellitus type 2. After initial evaluation and treatment with alpha-adrenergic blockade and propranolol, he again underwent surgery. In addition to peritoneal metastases confirmed to be caused by malignant phaeochromocytoma he also had a carcinoma of the caecum. The second patient, a 32-year-old woman, complained of headache and palpitations and had liver-enzyme disorders. Ultrasound examination revealed a tumour in the right upper abdomen and a recurrence of phaeochromocytoma was diagnosed; an intact pregnancy was also found. After a healthy son had been born by caesarian section, she underwent debulking of the large intra-abdominal lymph nodes and of two metastases in the lung. At the last follow-up she was under treatment with radioactive 123I-meta-iodobenzylguanidine (123-MIBG) because of residual metastases. Studies report recurrence ofphaeochromocytoma in 8-20% of cases, and such a recurrence may be either benign or malignant. Factors predictive for recurrence are older age, a malignant primary tumour, tumour weight above 60 g, extra-adrenal origin of the tumour and peroperative tumour spill. Long-term follow-up of patients is indicated, even after successful initial surgery.

Adrenal Gland Neoplasms↗

PubMed2006

Cyclical Cushing's syndrome due to an atypical thymic carcinoid.

A 43-year-old man presented with fluctuating symptoms of weight gain, shortness of breath, pretibial oedema, associated with anxiety and memory disturbances. Laboratory investigation revealed an adrenocorticotropin (ACTH)-dependent cyclical Cushing's syndrome characterised by remarkable variations in urinary cortisol excretions ranging from 27 to 28,050 nmol/ 24 h. Magnetic resonance imaging (MRI ) of the pituitary was normal and ectopic ACTH production was suspected. A tumour in the right anterior mediastinum was revealed on octreotide receptor scintigraphy, which had initially been overlooked on computed tomography (CT) scanning. A thymic carcinoid tumour was suspected, which was supported by increased levels of urinary serotonin, while platelet serotonin and urinary 5-hydroxyindoleacetic acid levels were normal. The tumour was removed surgically and histological examination revealed an atypical thymic carcinoid tumour. Postoperatively, the patient's symptoms disappeared rapidly. He underwent external radiotherapy and is still free of symptoms after almost two years of follow-up. For clinical practice, a cyclical Cushing's syndrome should be suspected in any patient with clinical signs of Cushing's syndrome but normal biochemistry. Repeated measurement of urinary cortisol excretion is then required to establish or rule out the diagnosis.

ACTH Syndrome, Ectopic↗

PubMed2005

[Pituitary apoplexy: an endocrinologic emergency].

A 32-year-old woman, a 73-year-old man and a 26-year-old pregnant woman presented with headache, vomiting, and variable presence of visual disturbances, impaired consciousness, and circulatory shock. All three had pituitary apoplexy. In the first patient lymphocytic hypophysitis was diagnosed, the second had a nonfunctional adenoma and the last patient probably also. All three patients were treated conservatively with full recovery of signs and symptoms. However pituitary insufficiency remained in all three. Pituitary apoplexy is an acute event with significant morbidity and mortality. The cause is a rapid expansion of, usually, a pre-existing, often not yet known, adenoma by massive haemorrhage or infarction. Pressure, among other things, causes hypopituitarism, meningism, compression of the chiasma opticum and visual disturbances. Although many predisposing factors have been identified, pituitary apoplexy is often an unpredictable event. Diagnosis is made by the typical clinical presentation, eye examination, MRI and by measuring pituitary hormones. Treatment is with suppletion of the deficient hormones and in selected patients by transsphenoidal decompression surgery.

Adenoma↗

PubMed2005

Hyperadrenocorticism in a dog due to ectopic secretion of adrenocorticotropic hormone.

Spontaneous hyperadrenocorticism in dogs is known to be the result of excessive secretion of adrenocorticotropic hormone (ACTH) by the pituitary gland or excessive autonomous glucocorticoid secretion by an adrenocortical tumor. Here, we report on an 8-year-old German shepherd dog in which ACTH-dependent hyperadrenocorticism was a result of ectopic ACTH secretion and could be related to an abdominal neuroendocrine tumor. Hyperadrenocorticism was diagnosed on the basis of the history, clinical signs, and elevated urinary corticoid/creatinine ratios (UCCRs; 236 and 350 x 10(-6); reference range < 10 x 10(-6)). The UCCR remained elevated (226 x 10(-6)) after three oral doses of dexamethasone (0.1 mg/kg body weight) at 8-h intervals. Ultrasonography revealed two equivalently enlarged adrenal glands, consistent with adrenocortical hyperplasia. Plasma ACTH concentration was clearly elevated (159 and 188 ng/l; reference range 5-85 ng/l). Computed tomography (CT) revealed that the pituitary was not enlarged. These findings were interpreted as indicating dexamethasone-resistant pituitary-dependent hyperadrenocorticism. Transsphenoidal hypophysectomy was performed but within 2 weeks after surgery, there was exacerbation of the clinical signs of hyperadrenocorticism. Plasma ACTH concentration (281 ng/l) and UCCRs (1518 and 2176 x 10(-6)) were even higher than before surgery. Histological examination of the pituitary gland revealed no neoplasia. Stimulation of the pituitary with corticotropin-releasing hormone did not affect plasma ACTH and cortisol concentrations. Treatment with trilostane was started and restored normocorticism. CT of the pituitary fossa, 10 months after hypophysectomy, revealed an empty sella. Hence, it was presumed that there was ectopic secretion of ACTH. CT of the abdomen revealed a mass in the region of the pancreas and a few nodules in the liver. Partial pancreatectomy with adjacent lymph node extirpation was performed and the liver nodules were biopsied. Histological examination revealed a metastasized neuroendocrine tumor. Abdominal surgery was not curative and medical treatment with trilostane was continued. At 18 months after the abdominal surgery, the dog is still in good condition. In conclusion, the combination of (1) severe dexamethasone-resistant hyperadrenocorticism with elevated circulating ACTH levels, (2) definitive demonstration of the absence of pituitary neoplasia, and (3) an abdominal neuroendocrine tumor allowed the diagnosis of ectopic ACTH secretion.

ACTH Syndrome, Ectopic↗

PubMed2004

Irregular and frequent cortisol secretory episodes with preserved diurnal rhythmicity in primary adrenal Cushing's syndrome.

To evaluate the pathophysiology of altered cortisol secretion in patients with primary adrenal hypercortisolism, cortisol secretion was investigated in 12 patients, seven with a unilateral adenoma and five with ACTH-independent macronodular adrenal hyperplasia compared with age- and gender-matched controls and with patients with pituitary-dependent hypercortisolism. Pulsatile secretion was increased 2-fold (P = 0.04), attributable to increased event frequency (P = 0.002). All patients showed a significant diurnal rhythm with a delay in phase shift of 3 h (P = 0.01). Approximate entropy ratio, a feedback-sensitive measure, was increased compared with controls (P = 0.00003) but similar to that of pituitary-dependent hypercortisolism (P = 0.77), denoting loss of autoregulation. Cortisol burst-mass tended to be smaller in patients with ACTH-independent macronodular adrenal hyperplasia than in unilateral adenoma (P = 0.06). In conclusion, increased cortisol secretion in patients with primary adrenal Cushing's syndrome is caused by amplified pulsatile secretion via event frequency modulation. We speculate that partial preservation of secretory regularity and diurnal rhythmicity point to incomplete autonomy of these tumors.

Adenoma↗

PubMed2004

[Swelling of lips as a first sign of acromegaly].

A 65-year-old female patient with swelling of lips and submandibular glands was referred to the department of Oral and Maxillofacial Surgery of an academic hospital. The patient was worried about her changed appearance and her general fatigue. This condition had not changed during the last six months, although she slept more. Despite extensive investigations her complaints could not be diagnosed as of oral or maxillofacial origin. She thereupon was referred to the department of internal Medicine to screen for an endocrine aetiology. Laboratory tests were positive for acromegaly.

Acromegaly↗

PubMed2002

[Endoscopic adrenal surgery: a new standard in 10 years].

OBJECTIVE: Description of the development of endoscopic adrenal surgery and the introduction of this procedure in Groningen University Hospital (GUH) and in the rest of the Netherlands. DESIGN: Literature overview, description of own results and results of a national survey. METHOD: Medline was searched with the search terms: 'laparoscopic', 'endoscopic' and 'adrenalectomy' for the period 1992-2001. During the period January 1998-July 2001, 39 patients underwent adrenal surgery at the GUH. A questionnaire about adrenal surgery was sent to 41 Dutch hospitals which provide surgical training. RESULTS: A total of 37 literature references were found, mostly prospective studies with a maximum of 130 patients, sometimes in retrospective comparison with conventional open surgery. No randomised studies were found. In the patient group at the GUH, 32 of the 39 patients had the adrenal gland removed endoscopically (82%). There were 3 (8%) primary open procedures due to tumour size (mean: 13 cm) and 4 (11%) conversions (mean tumour size: 6 cm). After 32 procedures, there was still a trend towards a shorter operation time. The response to the national survey was 88% (36/41). In 9% of the hospitals no adrenal surgery was performed. In the remaining hospitals minimally invasive adrenal surgery took place in about two-thirds of the patients, mainly via the retroperitoneal route (63%). More procedures were carried out in the university hospitals (mean: 11.6 per year) than in the non-university hospitals (mean: 2.9 per year). There were few concrete arrangements concerning the concentration of this technically demanding and rare procedure. CONCLUSION: Over the last 10 years endoscopic adrenalectomy has developed to become the new standard for the surgical removal of benign adrenal tumours with a diameter < 10 cm. Although the procedure has an evident learning curve, there are still few concrete arrangements in the Netherlands concerning the necessary concentration of this difficult and rare technique.

Adrenal Gland Neoplasms↗

PubMed1999

Increased episodic release and disorderliness of prolactin secretion in both micro- and macroprolactinomas.

To quantify prolactin (PRL) secretion patterns, ten untreated (female) microprolactinoma patients and six (male) macroprolactinoma patients underwent repetitive blood sampling every 10 min over 24 h. PRL release activity was analyzed from plasma PRL concentration (immunofluorimetric assay) profiles via a model-independent discrete peak detection program (Cluster) and a waveform-independent deconvolution technique (Pulse). Diurnal variations were analyzed by cosinor analysis. The number of distinct PRL pulses (mean +/- S.E.M.) was increased in patients: microprolactinoma 18.6 +/- 0.6/24 h versus female controls 12.4 +/- 0.6 (P = 6.7 x 10-s), and macroprolactinoma 18.0 +/- 0.9 versus male controls 13.5 +/- 0.8/24 h (P = 0.003). In patients, PRL pulse height, amplitude, pulse area and interpeak nadir concentrations were each greatly elevated compared with gender-matched controls. By 2-component deconvolution analysis, the mean nadir PRL secretion rate in microprolactinoma patients was augmented 20-fold at 0.408 +/- 0.089 microgram/l per min versus in female controls 0.019 +/- 0.009 microgram/l per min (P < 0.001); and in macroprolactinoma by 130-fold at 2.067 +/- 0.693 micrograms/l per min versus male controls 0.016 +/- 0.001 microgram/l per min (P = 0.001). Corresponding 24 h mean PRL secretion rates were in women, 0.658 +/- 0.147 and 0.044 +/- 0.018 (P < 0.001), and in men, 3.309 +/- 1.156 and 0.035 +/- 0.010 micrograms/l per min (P = 0.001), being respectively 15- and 94-fold increased in tumors. The estimated PRL production per day was 160 +/- 15 and 187 +/- 20 micrograms in male and female controls respectively. PRL production was 2860 +/- 640 micrograms in female patients with microadenomas (P < 0.001), and 37,800 +/- 5900 micrograms in male macroadenoma patients (P = 0.001). Cosinor analysis of the plasma concentrations revealed a significant rhythm in nine of ten, patients with a microadenoma, and in five of six with a macroadenoma. The same method applied to pulse height and amplitude disclosed a significant rhythm for PRL pulse height, but not for pulse amplitude, suggesting preserved rhythmicity of baseline interpulse nadir PRL concentrations. Approximate entropy (ApEn), a scale- and model-independent regularity statistic, averaged 1.6559 +/- 0.028 in microprolactinoma patients versus 0.8128 +/- 0.079 in female controls (P = 1.7 x 10(-8)); ApEn in macroadenomas was 1.5674 +/- 0.054 versus male controls 0.8773 +/- 0.076 (P = 1.7 x 10(-5), signifying greater secretory irregularity in the patients. Compared with microadenomas, macroadenomas exhibited a higher mean plasma concentration, overall mean PRL secretion rate, nadir secretion rate and pulse area, but similar peak frequency. We conclude that PRL secretion by prolactinomas is characterized by increased plasma PRL episodicity of release, increased total (15- to 100-fold) and basal (20- to 130-fold) secretion rates, and increased disorderlines of minute-to-minute secretion. These abnormalities of secretory control are very similar to those for GH and ACTH identified earlier in acromegaly and Cushing's disease respectively, thus suggesting mechanistic generality of pituitary tumor secretory derangements, independent of the particular hormone.

Adult↗

PubMed1998

Pituitary apoplexy in acromegaly, a long-term follow-up study in two patients.

Pituitary apoplexy is a serious complication in about 3% of patients with a pituitary adenoma. Very often, the diagnosis of a functioning or non-functioning adenoma is made in retrospect. In this report, we describe two patients in whom the diagnosis of acromegaly was made before the apoplexy. In one patient, surgical intervention was necessary because of remaining clinical and biochemical activity; in the other patient conservative follow-up was pursued. Seven and nine years after apoplexy, respectively, the patients were clinically and biochemically in remission. During the follow-up, three and five years after apoplexy, respectively, the patients underwent a 10-min venous sampling procedure for 24 hours, and the GH secretory profile was investigated with multiparameter deconvolution analysis and by approximate entropy (ApEn), a scale- and model-independent regularity measure. The deconvolution analysis revealed an increased basal (nonpulsatile) GH secretion rate, while the total 24 h secretion rate was normal compared with 13 healthy male control subjects. ApEn was much larger for each patient than for any control subject value, indicating markedly more irregular GH secretion. We hypothesize that these subtle abnormalities are caused by non-specific damage as a result of vascular insult, leading to abnormal vascular supply, or abnormal autocrine and paracrine GH regulation within the remaining gland.

Acromegaly↗

PubMed1998

Can intra-operative GH measurement in acromegalic subjects predict completeness of surgery?

OBJECTIVE: Results of trans-sphenoidal pituitary surgery, in terms of long-term cure, vary considerably between centres. Additional techniques, which can assist the neurosurgeon in deciding whether surgery is complete or not, might therefore be important. One such potential tool is the intra-operative measurement of GH and calculating the plasma half-life from the plasma samples obtained after the presumed complete resection of the adenoma. METHODS: GH half-life was calculated from 5-10 min plasma samples after adenomectomy in 20 patients. GH was measured with a sensitive and rapid IFMA, and the results could be reported within 30 min, but were not used in this study for per-operative decisions. Cure was defined by a glucose suppressed plasma GH concentration below 1 mU/l (0.38 microgram/l) during follow-up studies and a normal plasma IGFI concentration. RESULTS: In 13 cured patients the plasma half-life was 22.2 +/- 1.9 min (range 14-40.6). In three non-cured patients the plasma half-life could not be calculated, and in four other patients the plasma half-life was 35.8 +/- 5.9 min (range 25.8-51 min). By applying 25 min as the upper normal limit for the GH plasma half-life, the sensitivity was 77%, specificity 100%, and positive predictive value 100%. CONCLUSION: Per-operative plasma GH monitoring is a potentially useful tool for determining the completeness of trans-sphenoidal surgery in acromegaly.

Acromegaly↗

PubMed1998

Reduced disorderliness of growth hormone release in biochemically inactive acromegaly after pituitary surgery.

The episodicity of 24 h GH release was studied in 18 patients with active acromegaly, 12 patients 7-10 days after pituitary surgery, 14 patients long after operation (3-17 years), and 21 healthy gender- and age-matched control subjects, using a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). Blood samples were taken at 10-min intervals for 24 h, and plasma GH concentrations were measured by immunofluorometric assay (detection limit 11.5 ng/l). For this study we selected operated patients who were biochemically in remission, defined by normal circulating IGF-I and insulin-like growth factor-binding protein-3 (IGFBP-3) concentrations, normal glucose-suppressed plasma GH concentration (<0.38 microg/l), and the normalization of the paradoxical rise of GH to TRH or GnRH. In patients with active acromegaly ApEn was 1.23+/-0.04, with no overlap with the control subjects (P = 1.2 x 10[-16]), who had an ApEn of 0.40+/-0.04. ApEn in patients shortly after surgery was 0.71+/-0.09 (P < 0.001 vs controls), and long after surgery 0.56+/-0.05 (P < 0.011 vs controls). ApEn values in treated and untreated patients correlated significantly with the plasma concentration of IGF-I (r=0.531) and IGFBP-3 (r=0.598), and the log-transformed 24h GH secretion rate (r=0.749). Shortly after surgery only one-third of the patients had a normal ApEn value, whereas long after surgery about 70% of the patients had a normal ApEn value. Although ApEn eventually normalized in about 70% of the operated patients, the cause of the persistence of abnormal GH release in the remainder of the subjects is not known, and might reflect permanent hypothalamic-pituitary dysfunction or a very early recurrence of the somatotroph adenoma.

Acromegaly↗

PubMed1997

Greater disorderliness of ACTH and cortisol release accompanies pituitary-dependent Cushing's disease.

We investigated the episodicity of 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 25 healthy matched controls, with a recently introduced scale- and model-independent regularity statistic, approximate entropy (ApEn). The mean (+/-S.E.M.) ApEn value for plasma ACTH concentrations in Cushing's disease was 1.3817 +/- 0.033, and in controls 0.8394 +/- 0.049 (P < 10(-10)); for plasma cortisol concentrations the values were 1.4575 +/- 0.052 and 0.8637 +/- 0.020 respectively (P < 10(-10)), implying greater irregularity of release for both hormones in Cushing's subjects. The calculated sensitivity and specificity of ApEn for ACTH profiles were 94% and 100% respectively. For cortisol the sensitivity and specificity were both 100%. ApEn was not correlated with sex, age, or the total 24-h secretion rate of ACTH and cortisol in patients and controls. The increased ApEn in patients with Cushing's disease points to an increased disorderliness of ACTH and cortisol secretion compared with healthy controls. In conjunction with the available literature, we hypothesize more generally that autonomous endocrine tumors may be typified by reduced regularity, orderliness, or synchrony of the time structure of hormone release.

Adrenocorticotropic Hormone↗

PubMed1996

Females secrete growth hormone with more process irregularity than males in both humans and rats.

In humans, serum growth hormone (GH) concentrations are significantly higher in women than in men, but the neuroendocrine mechanisms that underlie such gender differences are not known. We compared normal episodic GH secretion in males and females in three distinct settings: two human studies employing quite different assay techniques (immunoradiometric assay and a high-sensitivity immunofluorimetric method) and a rat study. To quantify the amount of regularity in data, we utilized approximate entropy (ApEn), a scale- and model-independent statistic. In each study, females exhibited significantly greater statistical irregularity in GH concentration series than their male counterparts (P < 10(-3) for each human study, P < 10(-6) for the rat study), implying that mass and mode of GH secretion are regulated differently in males and females. The regularity comparisons indicated complete gender separation (100% specificity and sensitivity) for the rat study and nearly complete separation for the immunofluorimetric assay study. The consistency and statistical significance of these findings suggest that this gender difference may be broadly based within higher animals and that this may be readily evaluated objectively by analysis of ApEn.

Adult↗

PubMed1996

An amplitude-specific divergence in the pulsatile mode of growth hormone (GH) secretion underlies the gender difference in mean GH concentrations in men and premenopausal women.

Although many studies have discerned higher serum GH concentrations in women than in men, based on measurements of single random blood samples or integrated 24-h means, the neuroendocrine mechanisms that underlie such gender differences have not been defined. Such mechanisms might entail an increase in GH-secretory burst frequency, amplitude, or duration, heightened interpulse basal GH release, or a prolonged half-life of GH. These mechanisms can be distinguished by deconvolution analysis of appropriate GH time series. Earlier studies employed RIA or IRMA with sensitivities of 0.1-0.5 microgram/L, which result in frequently undetectable serum GH concentrations. To address these limitations, we undertook blood sampling at 10-min intervals for 24 h and applied a high-sensitivity immunofluorometric assay of GH (sensitivity 0.0115 microgram/L). Multiparameter deconvolution analysis was used to estimate specific features of GH secretion, while simultaneously calculating the half-life of endogenous GH. Eleven men and 11 premenopausal women from the same community were studied. Discrete peak detection by Cluster was employed as a complementary half-life-independent technique to assign variations in serum GH into pulsatile and basal fractions over 24 h. Cluster revealed significantly higher mean serum GH concentrations over 24 h in women (0.78 +/- 0.08 microgram/L) compared with in men (0.27 +/- 0.03 microgram/L, P < 0.00005). Women exhibited significantly higher maximal serum GH concentration peak values than men (2.08 +/- 0.34 microgram/L in women, 0.67 +/- 0.11 microgram/L in men, P = 0.0008), which could be, in turn, attributed to a significantly increased incremental serum GH peak amplitude (1.85 +/- 0.33 microgram/L in women vs. 0.60 +/- 0.10 microgram/L in men, P = 0.0021) and a longer peak duration (114 +/- 8 min in women, 86 +/- 4 min in men, P = 0.008). The mean area under the serum GH concentration peak was significantly (3-fold) higher in women than in men (98 +/- 17 micrograms/L.min in women, 34 +/- 8 micrograms/L.min in men, P = 0.0046). Serum GH peak frequency was similar in women (9.7 +/- 0.8 peak/24 h) and men (10.7 +/- 1.1 peak/24 h, P = NS). The mechanisms underlying the increase in serum GH concentration pulse amplitude, duration, and area were investigated further by deconvolution analysis. Deconvolution analysis disclosed equivalent secretory pulse frequencies in women and men (13 +/- 0.9 bursts/day in women, 10.5 +/- 1.3 bursts/day in men,P = NS), and statistically indistinguishable mean interburst intervals of 106 +/- 8 min in women and 150 +/- 26 min in men (P = NS). GH-secretory burst mass was significantly higher in women by approximately 2.4-fold (P = 0.0013) compared with in men, which was attributed to a greater burst amplitude. Only low levels of basal GH release were inferred in women (5%) and men (9%), which did not differ significantly between genders. Moreover, the calculated half-life of endogenous GH was no different in women compared with in men: 15.8 +/- 0.7 min vs. 17.1 +/- 0.8 min, respectively (P = NS). The calculated daily secretion rate was 3-fold higher in women (47 +/- 4.8 micrograms/L.24 h) than in men (15 +/- 1.8 micrograms/L.24 h) (P < 0.001). In summary, discrete peak-detection analysis of serum GH concentration profiles collected at 10-min intervals over 24 h in men and premenopausal women discloses significantly different mean serum GH concentrations that are accounted for by higher maximal and incremental serum GH peak amplitudes. Deconvolution analysis demonstrated that the mechanism supporting the amplitude-specific difference in women was an augmentation of the GH-secretory burst mass caused by a higher GH-secretory burst amplitude. These gender differences were highly specific because the frequency of detectable GH-secretory bursts, the calculated endogenous half-life, and the estimated basal GH release were no different in women than in men.

Adolescent↗

PubMed1995

Combined amplification of the pulsatile and basal modes of adrenocorticotropin and cortisol secretion in patients with Cushing's disease: evidence for decreased responsiveness of the adrenal glands.

We investigated 24-h ACTH and cortisol secretory profiles in 16 patients with Cushing's disease and 23 healthy controls. Blood samples were taken at 10-min intervals, and data were analyzed with a multiparameter deconvolution technique. The patients had the same number of ACTH pulses per 24 h as the controls (34 vs. 32/24 h) and similar plasma ACTH half-lives (17.4 +/- 0.7 vs. 19.3 +/- 0.5 min). The mass of ACTH secreted per pulse was increased, which was caused by an increased maximal secretion rate and prolonged secretion burst duration. The number of resolved cortisol pulses was less than that for ACTH, but higher in patients than in controls (24 vs. 17/24 h), with similar half-lives in both groups (57 +/- 2 vs. 59 +/- 4 min). The mass of cortisol secreted per pulse was higher in patients than in controls due to an increased maximal secretion rate attained within each burst. The mean total mass of 24-h cortisol production was 12.8 mg in controls (range, 6.7-20 mg) and 46 mg (range, 13.4-154) in patients. Basal secretion rates of ACTH and cortisol were increased 19-fold (ACTH) and 7-fold (cortisol) above control values in patients with Cushing's disease (P < 0.0002). The ratio of total 24-h cortisol and ACTH production (in mass units per L distribution volume) was 23 +/- 1.9 in controls and 11 +/- 2.3 in patients (P < 0.001). The secretory parameters for ACTH showed strong diurnal rhythms in control subjects, but were not significant in six patients. Diurnal rhythms for cortisol could be detected in only five patients. From these observations we conclude that cortisol and ACTH release in Cushing's disease is highly pulsatile, with the preservation of diurnal properties in only some patients. Markedly amplified total daily hormone secretion was attributed to a 19-fold (ACTH) and 7-fold (cortisol) higher basal secretion rate, increased secretory burst mass (ACTH and cortisol), and frequency (cortisol) in Cushing's disease. In addition, the apparent response of the adrenal gland to increased ACTH levels is diminished, suggesting decreased responsiveness of the adrenal glands.

Adrenal Glands↗

PubMed1994

Growth hormone secretion in recently operated acromegalic patients.

GH secretion patterns were studied in 14 recently transsphenoidally operated patients by measuring GH concentrations in blood sampled every 10 min over 24 h with a highly sensitive time-resolved immuno-fluorescent assay. Plasma GH concentrations were analyzed with a discrete peak detection program (Cluster) and a multiparameter deconvolution technique. Diurnal variations were analyzed by cosinor analysis. Nine or 10 days after pituitary surgery all patients had a normal plasma insulin-like growth factor-I level, and GH levels were suppressed to below 1.25 micrograms/L in 13 patients and to 1.3 micrograms/L in 1 subject during an oral glucose tolerance test. As we found a highly significant difference in GH secretion between male and female controls, the results obtained in patients were compared with those in their gender- and age-matched controls. Patients with active acromegaly displayed a significantly higher number of deconvolution-estimated secretory bursts (31/24 h in males and 27/24 h in female patients). The estimated secretion rate per 24 h was 25 times greater in female acromegalics and 100 times greater in male acromegalics than that in the controls. In patients with active acromegaly, about 50% of the GH was secreted in a nonpulsatile fashion. In contrast, normal subjects and patients shortly after pituitary surgery secreted GH predominantly (> 99%) in a pulsatile manner. By deconvolution analysis, the mean plasma half-life of GH was 19.7 min in treated male patients and 19.5 min in treated female patients (P = NS vs. controls) estimated mean total GH production/day, 188 micrograms in males and 240 micrograms in females (P = NS vs. controls); number of secretory bursts/24 h, 19.3 in males and 21.9 in females (P = NS vs. controls). In addition, we could not establish any difference in pulse characteristics with Cluster analysis between surgically treated patients and their control subjects. The present data suggest that the basic abnormality of acromegaly resides in the pituitary gland rather than in the hypothalamus.

Acromegaly↗

PubMed1993

Sex-dependent alteration in cortisol response to endogenous adrenocorticotropin.

We have investigated ACTH and cortisol secretion patterns in two groups of five healthy adult male and female subjects. Plasma samples were obtained at 10-min intervals for 24 h, and pulsatile hormone release was analyzed by a multiparameter deconvolution technique. ACTH secretion was greater in male than female subjects; the production rate per 24 h was 139 +/- 7 pmol/L distribution volume in males, and 89 +/- 11 pmol/L distribution volume in females (P = 0.007). Cortisol secretion did not differ significantly between sexes; in males, the 24-h secretion rate was 2807 +/- 239 nmol/L distribution volume, and in females, it was 2970 +/- 411 nmol/L distribution volume (P = NS). The number of ACTH secretory pulses per 24 h, as determined by deconvolution analysis, was 16.2 +/- 1.4 in males and 19.6 +/- 2.0 in females (P = NS). There were no sex differences in the number of cortisol pulses or the calculated half-lives of ACTH and cortisol. ACTH and cortisol pulses were significantly concordant at a cortisol lag time of 10 min, as demonstrated by probability analysis and cross-correlation with auto-regressive modeling. Based on a significantly different regression intercept of cortisol pulse height on ACTH pulse height in women than in men (P < 0.001) and a higher ratio of cortisol to ACTH production rates in women than in men (P = 0.013), we suggest that the female adrenal cortex is more responsive to ACTH than its male counterpart in terms of glucocorticoid production. Consequently, equivalent daily cortisol secretion rates are attained in men and women at the expense of greater ACTH release in men.

Adrenocorticotropic Hormone↗

PubMed1992

Influence of single- and multiple-dose omeprazole treatment on nifedipine pharmacokinetics and effects in healthy subjects.

The effects of single dose (20 mg) and short-term (20 mg/day for 8 days) oral treatment with omeprazole on the pharmacokinetics and effects of oral nifedipine (10 mg capsule) and on gastric pH have been investigated in a randomized, double-blind, placebo-controlled cross-over study in 10 non-smoking healthy male subjects. The single dose of omeprazole had no significant effect on any pharmacokinetic parameter of nifedipine, nor on gastric pH, or blood pressure or heart rate. Short-term omeprazole treatment increased the AUC of nifedipine by 26% (95% confidence interval 9-46%), but all other pharmacokinetic parameters of nifedipine, including elimination half-life, Cmax, tmax, and recovery of the main urinary metabolite, were not significantly changed. The median gastric pH during the absorption phase of nifedipine was increased by short-term omeprazole (pH 4.2) compared to placebo treatment (pH 1.4). Blood pressure and heart rate did not differ between treatments. The interaction between nifedipine and omeprazole is not likely to be of major clinical relevance.

Adult↗