Success rate of thyroid remnant ablation for differentiated thyroid cancer based on 5550 MBq post-therapy scan.

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.

Transsphenoidal pituitary surgery via the endoscopic technique: results in 35 consecutive patients with Cushing's disease.

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.

Massive reduction of tumour load and normalisation of hyperprolactinaemia after high dose cabergoline in metastasised prolactinoma causing thoracic syringomyelia.

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.

[Hypertension: once primary, always primary?]. / Hypertensie: eens primair, altijd primair?

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.

[Diagnostic image (72). An adult woman with coarsening of the face. Acromegaly]. / Diagnose in beeld (72). Een volwassen vrouw met vergroving van het gelaat. Acromegalie.

A 45-year-old woman with acromegaly went into remission after pituitary surgery.

Management of Nelson's syndrome: observations in fifteen patients.

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.

[Clinical presentation, treatment, and follow-up of 32 patients with a primary intracranial germinoma, registered during the previous 15 years in the Dutch Pathological-Anatomical National Automated Archive (PALGA)]. / Kliniek, behandeling en follow-up van 32 patiënten met een primair intracranieel germinoom uit de afgelopen 15 jaar, geregistreerd in het Pathologisch-Anatomisch Landelijk Geautomatiseerd Archief (PALGA).

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.

Follow-up regimen of differentiated thyroid carcinoma in thyroidectomized patients after thyroid hormone withdrawal.

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.

Gender difference in insulin-like growth factor I response to growth hormone (GH) treatment in GH-deficient adults: role of sex hormone replacement.

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.

Body composition determined by six different methods in women bilaterally adrenalectomized for treatment of Cushing's disease.

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.

Progression of a Nelson's adenoma to pituitary carcinoma; a case report and review of the literature.

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.

Preclinical Cushing's syndrome in patients with an adrenal incidentaloma.

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.

Bone mineral density and bone turnover before and after surgical cure of Cushing's syndrome.

We measured bone mineral density (BMD) using dual-energy x-ray absorptiometry in 20 patients with Cushing's syndrome (CS) (14 pre- and 2 postmenopausal women, 4 men) before and in 18 of them also at regular intervals after surgical cure (median duration of follow-up, 36 months). In addition, in the premenopausal women with CS, fasting blood samples and 2-h fasting urine samples for measurement of biochemical parameters of bone and collagen metabolism were collected before and in 9 of them also at regular intervals during the first 2 yr after surgery. Marked osteopenia was present in most patients with active CS (Z-scores: lumbar spine -1.45 +/- 1.44 and femoral neck -1.50 +/- 1.02; mean +/- SD). No consistent change in BMD was observed at 3 and 6 months after surgery. Thereafter BMD increased considerably in almost all patients. For the 15 patients with a follow-up of at least 1 yr, Z-scores at the last evaluation were -0.65 +/- 1.27 for the lumbar spine and -0.98 +/- 1.02 for the femoral neck (both P < 0.002 compared with pretreatment values). In the premenopausal patients, the increase in BMD both in the lumbar spine and in the femoral neck at 24 months was inversely correlated with age (r = -0.733, P < 0.03, and r = -0.667, P < 0.05, respectively). Serum levels of osteocalcin, bone alkaline phosphatase, carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and the cross-linked telopeptide of type I collagen were not significantly different between the group of 14 premenopausal patients with active CS and a control group of 18 age-matched healthy premenopausal women. However, the urinary hydroxyproline/creatinine ratio was significantly higher in patients with CS (24.6 +/- 9.6 vs. 16.2 +/- 3.5 mumol/mmol, P < 0.01). In all 9 premenopausal patients, serum levels of osteocalcin increased considerably between 0 and 3 months (from 1.04 +/- 0.20 to 3.82 +/- 0.30 nmol/L) (mean +/- SEM, P < 0.0001), indicating a prompt increase of osteoblast activity. Also serum levels of carboxyterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen, and cross-linked telopeptide of type I collagen, and the urinary hydroxyproline/creatinine ratio increased significantly between 0 and 3 months. Thereafter these levels decreased gradually. We conclude that marked osteopenia in the lumbar spine and femoral neck is present in most patients with active Cushing's syndrome.(ABSTRACT TRUNCATED AT 400 WORDS)

Predictive value of luteinizing hormone releasing hormone (LHRH) bolus testing before and after 36-hour pulsatile LHRH administration in the differential diagnosis of constitutional delay of puberty and male hypogonadotropic hypogonadism.

Intravenous LHRH bolus testing (100 micrograms) after 36 h of pulsatile LHRH administration (5 micrograms/90 min) preliminary has been reported to allow complete differentiation between constitutional delay of puberty (DP) and hypogonadotropic hypogonadism (HH) in a small group of sexually immature patients. So far, these data have never been confirmed. To assess the discriminatory power of the test, 33 patients with a presumptive diagnosis of either DP (n = 17) or HH (n = 16), confirmed by clinical follow-up, were studied accordingly. Both groups of patients had similar mean basal LH and FSH levels (P > 0.10). The mean basal plasma testosterone level was three times higher in DP than in HH (4.2 +/- 1.0 vs. 1.4 +/- 0.2 nmol/L, P* < 0.001), but there was a wide overlap. In response to the first LHRH bolus test, the mean LH increment was significantly lower in HH than in DP patients (P < 0.001), but, in 44% of the patients, the values overlapped. The FSH increments were similar in HH and DP. Pulsatile LHRH administration for 36 h similarly increased LH levels in HH and DP to values (2.7 +/- 0.4 and 3.8 +/- 0.5, respectively) slightly higher than before (P < 0.01), but again, not statistically significantly different from each other. The mean testosterone levels increased 2-fold in both groups and remained significantly higher in DP than in HH (7.6 +/- 2.1 vs. 2.8 +/- 0.5 nmol/L P* < 0.05). The mean FSH levels after priming also rose, however, to levels significantly higher in HH than in DP (5.2 +/- 0.8 vs. 3.5 +/- 0.4, P* < 0.05). In HH the ratio of FSH to LH almost doubled, whereas it virtually remained unchanged in DP. LHRH bolus testing after LHRH priming evoked a significantly lower LH response in both HH and DP than before priming despite only slightly higher baseline LH values. The LH increment in HH was five times lower in HH than in DP. In any of the 16 HH patients, the LH increment was < or = 3 IU/L, whereas in 15 out of 17 DP patients the increase was higher (sensitivity of the test 100%, specificity 88%, and diagnostic efficiency 94% after LHRH priming against 56%, 94%, and 75% respectively, before LHRH priming.(ABSTRACT TRUNCATED AT 400 WORDS)

[Compared to whole body scanning thyroglobulin assay is reliable in the follow-up of thyroidectomized patients with thyroid carcinoma]. / Thyreoglobulinebepaling goed bruikbaar in de follow-up van schildkliercarcinoompatiënten na thyreoïdectomie, in vergelijking met lichaamsscintigrafie.

OBJECTIVE: To determine whether it is reliable to do thyroglobulin measurements during thyroid hormone substitution (Tg ON) alone or whether it is also necessary to do 131I total body scanning (TBS) and Tg measurements after withdrawal of thyroid hormone substitution (Tg OFF) in the follow-up of patients with differentiated thyroid carcinoma. DESIGN: Retrospective. SETTING: University Hospital Nijmegen. METHODS: 202 Patients (151 females and 51 males, mean age 50.6 years) with differentiated thyroid carcinoma were examined in the period 1970-90. All patients had undergone total thyroidectomy and if necessary 131I ablation. 27 Patients with Tg antibodies were excluded (13.4%). In 175 patients Tg OFF levels were compared with TBS and clinical and radiological data. In 81 of them Tg ON levels were also compared. RESULTS: Specificity of Tg OFF and Tg ON measurement was 83 and 88%. Sensitivity of Tg OFF and Tg ON measurement was 100 and 92%. In detecting local residual thyroid tissue Tg OFF was superior to Tg ON. In detecting metastases Tg OFF and Tg ON were both superior to TBS. CONCLUSION: In the follow-up of patients with differentiated thyroid carcinoma it is reliable to do Tg measurements during thyroid hormone suppression. When Tg ON is detectable (> 3 pmol/l) TBS and Tg OFF measurement and if necessary further investigations have to be performed.

Unpredictable hypersecretion of cortisol in Cushing's disease: detection by daily salivary cortisol measurements.

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.

Postprandial gallbladder motility and plasma cholecystokinin at regular time intervals after injection of octreotide in acromegalics on long-term treatment.

The increased risk of gallstone formation in acromegalics treated with the somatostatin analog octreotide has been related to an impaired gallbladder emptying. To determine the duration of these inhibitory effects, meal-stimulated gallbladder motility, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in five acromegalics treated for 6-32 months with 200-300 micrograms octreotide daily. Meal tests were performed 45 min, 8 hr and two weeks after the last 100-micrograms subcutaneous dose. Results were compared with those in normal subjects. Integrated postprandial gallbladder contraction (-125 +/- 194 cm3/120 min) and integrated PP secretion (-0.1 +/- 0.2 nmol/liter/120 min) were completely suppressed in the 45-min study, but significantly improved (P < 0.05) when measured 8 hr (1376 +/- 322 cm3/120 min and 3.0 +/- 1.0 nmol/liter/120 min) and two weeks (1437 +/- 263 cm3/120 min and 10.6 +/- 1.6 nmol/liter/120 min) after the last dose of octreotide. The integrated gallbladder contraction in acromegalics at 8 hr was comparable to that at two weeks and to that in normal subjects, but the integrated PP response at 8 hr was significantly smaller (P < 0.05 vs two weeks and vs normals). Integrated plasma CCK secretion at 45 min (0.13 +/- 0.06 nmol/liter/120 min) was not statistically significantly different from the response at 8 hr (0.15 +/- 0.02 nmol/liter/120 min) and from that in normal subjects, but it was significantly increased at two weeks after cessation of octreotide (P < 0.05 vs 45 min and 8 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

Dose intensity of chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil in the elderly with advanced breast cancer.

Toxicity and results of two different dose levels of chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) in older (greater than 70 years) patients with advanced breast cancer were evaluated in a prospective (non-randomised) study. During the first three courses of chemotherapy dose reduction for haematological toxicity was necessary in all of 10 and 8 of 13 patients treated with an intended dose of 100% and 75% of standard dose CMF, respectively. The median percentages of CMF, administered during the first three courses were about 75% in both groups of patients corresponding with a median dose intensity of 72% (range 49-87%) and 64% (range 36-78%) for patients of the 100% and 75% dose group, respectively. In 34 younger postmenopausal women (mean age 57 years) treated in our institution for advanced breast cancer the median percentages of CMF in the second and third course were 86% and 84%, respectively with a median dose intensity during the three courses of 82%. Dose reductions of CMF and bone marrow toxicity, though interdependent, were statistically significantly correlated with the endogenous creatinine clearance, but not with age. 1 patient died during severe leukopenia and thrombocytopenia. Non-haematological side effects were most pronounced in the 100% group. Results of therapy in both groups of patients were about equal and compared well with those of CMF therapy in general. It is advised that the dose of CMF in patients above 70 years should not exceed 75% of standard dose. Further dose reduction of methotrexate in case of severe renal failure is required.

Poikilothermia in man: pathophysiology and clinical implications.

Poikilothermia, the inability to maintain a constant core temperature independent of ambient temperature, markedly influences both the mental and physical function of affected patients; furthermore, prolonged hypothermia can induce numerous complications. To establish the pathophysiology of thermoregulation underlying poikilothermia in man, we compared 4 women with acquired poikilothermia, with 9 female control subjects. The activity of the main thermoregulatory effector mechanisms was assessed in a thermoneutral environment, and during subsequent cold stress and heat exposure. At thermoneutrality the patients had a significantly lower rectal temperature and resting metabolic rate compared with the controls; no patient showed peripheral vasoconstriction or shivering. Cooling revealed markedly reduced peripheral vasoconstriction in 3 patients and failure of the metabolic response in 2 patients; unlike controls, no patient exhibited shivering. Heat challenge revealed severely reduced capacity for heat dissipation in all patients. We conclude that in patients with poikilothermia, the mechanisms for both heat conservation and heat dissipation are seriously attenuated. Careful monitoring of the core temperature and adequate measures to maintain normothermia are of great importance in patients with poikilothermia in order to provide adequate treatment, improve the quality of life, and prevent serious complications.