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OBJECTIVE: Treatment with somatostatin analogues is the primary medical treatment of acromegaly. Controversies still exist whether acute octreotide effect predicts long-term biochemical effects, tumour regression or surgical cure. This prospective study investigates effect of 6-month treatment with octreotide long-acting repeatable (LAR) on insulin-like growth factor-1 (IGF-1) and growth hormone (GH) levels, pituitary function, tumour regression and postoperative cure in de novo acromegalic patients. DESIGN AND METHODS: After a baseline evaluation including fasting hormone levels, MRI scan and an acute 50 µg octreotide test, 32 patients were treated with octreotide LAR 20 mg every 28th day for 6 months before surgery. Treatment effects on IGF-1 and GH levels, serum hormone levels and tumour volume were monitored. Surgical cure was evaluated 3 months postoperatively. RESULTS: Mean tumour volume reduction was 35%, in one-third of the patients more than 50%, while approximately one-third achieved biochemical remission evaluated by normalized IGF-1 levels. The GH reduction following an acute octreotide test was 81 ± 19% and associated with long-term GH reduction (r = 0·78, P < 0·0005). However, neither acute (r = 0·29, P = 0·12) nor the long-term octreotide effect (r = 0·11, P = 0·58) on GH levels was associated with tumour volume reduction and did not predict subsequent surgical cure. CONCLUSION: Six months of long-acting octreotide using a fixed dose, 1/3 of the patients came in biochemical remission, while 2/3 had significant tumour reduction. Moreover, an acute effect of octreotide seemed to be a prerequisite for long-term effect.

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OBJECTIVE: Gamma knife radiosurgery (GKR) can be used as primary or adjuvant therapy for the treatment of an ACTH-producing pituitary tumor after bilateral adrenalectomy, called Nelson syndrome (NS). We have examined the effect of GKR on tumor growth and ACTH-hypersecretion, and characterized the adverse events of this treatment in patients with NS. DESIGN: Cross-sectional follow-up study. First, retrospective data pre- and post-GKR were collected. Patients then underwent a predefined survey including radiological, endocrinological, ophthalmological, and neurosurgical evaluation. SUBJECTS: Ten patients treated with GKR for NS after previous bilateral adrenalectomy. The mean follow-up was 7 years. No patient was lost to follow-up. RESULTS: Tumor growth was stopped in all patients. The ACTH levels declined in eight patients, and normalized in one patient. There was a significant drop in ACTH levels, with a half-time of 2.8 years. No patient developed visual field defects or any other cranial nerve dysfunction as a result of treatment. Four patients started hormone substitution therapy during the follow-up period. The substitution therapy of three pituitary axes present at GKR treatment could be stopped during the same period. One patient developed a glioblastoma in the left parieto-occipital region 14 years after GKR, far from the field of treatment. As the radiation level was below 1Gy to this area, it is unlikely that the GKR treatment itself induced the malignant tumor. CONCLUSION: In patients with NS, GKR is an effective adjuvant treatment, carrying relatively few adverse effects. Although the risk of developing a secondary neoplasia after GKR is present, it is probably extremely low.

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CONTEXT: Surgery is the primary treatment of acromegaly. However, it often fails to cure the patient. New strategies that improve surgical outcome are needed. OBJECTIVE: Our objective was to investigate whether 6-month preoperative treatment with octreotide improves the surgical outcome in newly diagnosed acromegalic patients. PATIENTS: During a 5-yr period (1999-2004), all newly diagnosed acromegalic patients between 18 and 80 yr of age in Norway were screened and invited to participate in the study. A total of 62 patients was included in the Preoperative Octreotide Treatment of Acromegaly study. RESEARCH DESIGN AND METHODS: After a baseline evaluation, patients were randomized directly to transsphenoidal surgery (n = 30) or pretreatment with octreotide (n = 32) 20 mg im every 28th day for 6 months before transsphenoidal surgery. Cure was evaluated 3 months postoperatively primarily by IGF-I levels. RESULTS: According to the IGF-I criteria, 14 of 31 (45%) pretreated patients vs. seven of 30 (23%) patients with direct surgery were cured by surgery (P = 0.11). In patients with microadenomas (< or = 10 mm), one of five (20%) pretreated vs. three of five (60%) with direct surgery were cured (P = 0.52). In patients with macroadenomas, 13 of 26 (50%) pretreated vs. four of 25 (16%) with direct surgery were cured (P = 0.017). CONCLUSIONS: Six-month preoperative octreotide treatment might improve surgical cure rate in newly diagnosed acromegalic patients with macroadenomas. These results have to be confirmed in future studies.

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BACKGROUND: Gamma knife radiosurgery (GKR) is an adjuvant treatment for acromegaly if surgery fails to normalize GH hypersecretion. OBJECTIVE: To examine the effect of GKR on tumor growth and hypersecretion, and to characterize the adverse effect of this treatment. DESIGN: Cross-sectional follow-up study. First, retrospective data pre- and post-GKR were collected. PATIENTS then underwent a predefined survey including radiological, endocrinological, ophthalmological, and neurosurgical evaluation. SETTING: Norwegian National Center for gamma knife treatment. PATIENTS: Sixty-one patients treated with GKR for acromegaly. Out of 55, 53 living patients underwent a detailed survey. The mean follow-up was 5.5 years. No patient was lost to follow-up. RESULTS: Tumor growth was stopped in all patients. At 3, 5, and 10 years after GKR, 45, 58, and 86% of patients had normal IGF-I levels. Consecutive hormone value analysis showed that patients receiving GH-suppressive medication had a more rapid decline in hypersecretion than those who did not receive such medication. Evaluated by survey baseline values alone, non-elevated IGF-I and GH levels below 5 mIU/l were found in 38%. GH-suppressive medication was terminated in 16 out of 40 patients following GKR. Nine out of 53 surveyed patients (17%) had normal IGF-I and GH nadir below 2.6 mIU/l at glucose tolerance tests, while not on hormone-suppressive medication. Two patients developed minor visual field defects. Eight patients started hormone substitution therapy during the follow-up period. CONCLUSION: GKR is an effective adjuvant treatment for residual acromegaly, carrying few side effects.

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CONTEXT: The clinical presentation of primary hyperparathyroidism (pHPT) has changed during the last half century, and the diagnosis is now more often made by chance in patients with no specific symptoms. OBJECTIVE: The present study is a randomized, controlled trial that investigates the effects of parathyroidectomy or medical observation in mild asymptomatic pHPT on morbidity and quality of life (QoL). DESIGN/SETTING/PATIENTS: A total of 191 patients (26 men) with asymptomatic pHPT [mean age 64.2 +/- 7.4 (sd) yr] were recruited in the study and randomized to medical observation (serum calcium level 2.69 +/- 0.08 mmol/liter) or surgery (2.70 +/- 0.08 mmol/liter). We here report baseline and 1 (n = 119) and 2 yr data (n = 99) on those who had completed the follow-up visits by the end of the inclusion period. RESULTS: At baseline, the patients had significantly lower QoL (SF-36) and more psychological symptoms, compared with age- and sex-matched healthy subjects. The two groups were similar at baseline, and no clinically significant changes in these parameters were seen during the observation time. Calcium and PTH normalized after surgery. The areal bone mineral density increased in the group randomized to operation, whereas the bone mineral density remained stable in the medical observation group. No change in kidney function (creatinine) or blood pressure was observed longitudinally or between the groups. CONCLUSIONS: Asymptomatic patients with mild pHPT have decreased QoL and more psychological symptoms than normal controls. No benefit of operative treatment, compared with medical observation, was found on these measures so far.

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BACKGROUND: Transsphenoidal surgical treatment is established as a treatment of hormonally active pituitary tumours, except prolactinomas. The cure rates in studies of large series of patients are varying. The volume of patients at Haukeland University Hospital, Bergen is limited, and in order to maintain sufficient experience, one surgeon performs all procedures. The aim of this study was to study the rates of cure and complications in patients who had undergone this procedure. METHODS: We did a retrospective survey evaluating the operative results of one surgeon operating hormonally active pituitary tumours from 1993 through 2002 at Haukeland University Hospital. Data were collected from medical and surgical case records. RESULTS: Primary surgery cured 37 out of 57 patients. There were 13 complications, including one death in hospital. Twenty patients received additional treatment with surgery, radiation therapy, or adrenalectomy. Thirteen of these patients received medical treatment with either somatostatin analogues or dopamine agonists. INTERPRETATION: Our study indicates that one surgeon can achieve results for transsphenoidal surgery that are on par with results reported from larger centres.

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BACKGROUND: Untreated endogenous Cushing's syndrome is a serious condition with high morbidity and mortality. New diagnostic procedures make today's assessment more accurate. We describe which tests should be done when there is suspicion of the syndrome. Treatment options are mentioned. MATERIAL AND METHODS: The paper is based on current international literature and reflects the experience of the authors. RESULTS AND INTERPRETATION: Endogenous Cushing's syndrome is caused by elevated cortisol levels. The reason can be overproduction of ACTH or an adrenocortical pathology. It should be considered when combinations of symptoms like central obesity, proximal muscle weakness, striae and menstrual irregularities are seen. Osteoporosis and impotence are other important symptoms. Diagnosis of Cushing's syndrome is often challenging. Measurement of urinary free cortisol or overnight dexamethasone suppression test has usually been performed initially. Midnight salivary cortisol seems promising as an alternative. The final diagnosis is often made after a combined evaluation of dynamic tests. The first-line treatment of endogenous Cushing's syndrome is surgery.

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The aim of this study was to compare bone mineral density (BMD) in a population-based sample of middle-aged and older Norwegians, with reference values provided by the manufacturer of the densitometer (Lunar) in order to evaluate whether these reference values are suitable for Norwegians. Additional aims were to estimate the prevalence of osteoporosis. Bone mineral density of the hip and total body was measured by dual-energy X-ray absorptiometry in 2303 men and 3105 women 47-50 and 71-75 years old, respectively, in western Norway, as part of the Hordaland Health Study (HUSK). Of these, 3403 white individuals were free of medications or diseases known to influence bone metabolism (reference group). Compared with the Lunar reference population, men and older women had a slightly but significantly lower BMD of trochanter and total femur and middle aged women had significantly higher total body BMD. Except for the higher mean BMD of total body among middle-aged women and the uniformly lower BMD values of Ward's triangle, the deviations from the reference values of the manufacturer were less than 4%. Approximately 2.6% of middle-aged men vs 0.9% of middle-aged women were classified as osteoporotic on the basis of BMD of femoral neck. While the BMD values for femoral neck in this healthy Norwegian population are similar to the reference population of Lunar, the values of trochanter and total femur are lower in all groups except middle-aged women; however, the discrepancies are not of sufficient magnitude to warrant rejection of this commonly used database among Norwegians. Use of the young adult means from the Lunar reference database classified a higher proportion of middle-aged men than women as osteoporotic and osteopenic.

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BACKGROUND: This paper surveys hormonally inactive pituitary tumours on the basis of the current international literature; it also reflects the experience of the authors. INTERPRETATION: Pituitary tumours are frequently diagnosed and usually show a low potential for growth. Although benign they may invade adjacent structures such as the cavernous and sphenoid sinuses. The diagnosis is usually made on the basis of pituitary failure or visual problems, or incidentally. Tumour debulking or removal, usually by transsphenoidal surgery, is indicated if there is a compression of the optic chiasm or if the tumour shows signs of growth on consecutive MRI scans. Surgery is an effective treatment of these tumours, with little risk of complications. Repeated surgery, either transsphenoidally or by craniotomy, is indicated if chiasmal decompression is not achieved initially. Fractionated single beam irradiation or stereotactic radiosurgery is indicated in cases where there is a residual of growing tumours that may not be removed surgically.

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OBJECTIVE: To investigate the effect of different antithyroid drug (ATD) regimens on relapse rates of Graves' disease, and to look for predictors of relapse. DESIGN AND METHODS: In a prospective two-way factorial randomized clinical trial, 218 patients with Graves' disease were assigned to ATD combined with l-thyroxine (l-T(4)) or ATD alone for 12 Months. After discontinuation of antithyroid therapy, each group was stratified to either 12 Months further treatment with l-T(4) or no treatment. Clinical and biochemical assessments were carried out before treatment, after 3 and 6 weeks, and every third Month for 12 Months. If the patients lacked symptoms of relapse, laboratory tests were performed every third Month for the second Year, and thereafter annually. RESULTS: The proportion of all patients with relapse was 47.7% 2 Years after withdrawal of ATD. There was no difference in relapse rates between the treatment groups (P=0.217, log--rank test). Smokers had a higher relapse rate than non-smokers (58.4% vs 38.8%, P=0.009). Patients who were thyrotropin-receptor antibody (TRAb) positive after 12 Months of antithyroid therapy had a higher relapse rate than those who were negative (72.5% vs 36.8%, P<0.0001). Similarly, relapse was more frequent (55.5%) in patients having large goiter compared with subjects with small goiter (36.3%, P=0.0007). CONCLUSIONS: Relapse rates of Graves' disease were independent of ATD regimen whether followed by l-T(4) therapy or not. Smoking, large goiter and presence of TRAb at the end of ATD therapy were strong predictors of relapse.

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BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a complication of hyperthyroidism. MATERIALS AND METHODS: We describe two patients with TPP. RESULTS: A 26-year-old man from Vietnam had weight loss, tachycardia, palpitations and heat intolerance for five months. Episodic leg and arm weakness developed three months after debut of symptoms. The second patient, a 23-year old woman from the Philippines, had had episodic leg weakness in the evenings after dinner for three weeks. Her attacks resolved spontaneously overnight. Physical examination of both patients revealed tachycardia and symmetrical proximal weakness involving both arms and legs. ECG and electrolyte analysis indicated a severe hypokalaemia; thyroid function tests showed hyperthyroidism. Both patients were diagnosed as having Graves' thyrotoxicosis and TPP. They were initially treated with propranolol and subsequently with carbimazole. The first patient had recurrence of thyrotoxicosis and paralysis after 16 months, whereas the second patient has remained symptom-free. INTERPRETATION: TPP is most common in Asian males, very few cases are reported in females. In Western countries TPP is rare, but with increasing immigration, TPP is likely to occur more frequently.

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BACKGROUND: Prolactinoma represents the most commonly occurring hormone-secreting pituitary adenoma. The majority of prolactinomas are small, only rarely do we find larger prolactinomas, so-called macroadenomas. They are almost exclusively benign. The symptoms are mainly caused by elevated prolactin levels and result in changes to the reproductive and sexual function. In cases of macroprolactinomas, symptoms caused by local mass effects can be seen. A variety of other conditions may also cause hyperprolactinaemia; the goal of the examination is to identify the cause. MATERIAL AND METHODS: We have reviewed recent literature and compared findings with current management of hyperprolactinaemia and prolactinoma in Norwegian university hospitals. RESULTS AND INTERPRETATION: The primary treatment is medical, intended to normalize prolactin levels, restore gonadal function, and reduce tumour size. With the new selective dopamine agonists, the treatment is often simple and efficient, but not all patients are in need of treatment.

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We describe a 23-year-old woman with a 3-week history of episodic leg weakness. The onset of weakness always occurred in the evening after dinner and the attacks resolved spontaneously by morning. Physical examination revealed a resting tachycardia and symmetrical, proximal weakness involving both arms and legs. Electrocardiogram (ECG) and electrolyte analysis showed a severe hypokalemia and thyroid function tests showed hyperthyroidism. The patient was diagnosed as having Graves' thyrotoxicosis and thyrotoxic periodic paralysis (TPP) and was initially treated with propranolol and subsequently carbimazole. No recurrence of the paralysis has been noted. TPP is most common in males of Asian extraction and is rare in women even in the Asian population. With increasing immigration, TPP is likely to occur more frequently in both Europe and North America and awareness of the condition is vital. Treatment of the underlying thyroid dysfunction cures the muscle symptoms.

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