ICAR: endoscopic skull‐base surgery

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Rathke's cleft cysts.

Rathke's cleft cysts (RCCs) are benign, sellar and/or suprasellar lesions originating from the remnants of Rathke's pouch. Although a common finding in routine autopsies (12-33% of normal pituitary glands), symptomatic cases are rare and comprise 5-15% of all surgically resected sellar lesions. Small, asymptomatic RCC do not require surgical intervention, and their natural history is not clear. In series of nonoperated presumed RCCs, 26-94% did not progress during follow-up periods up to 9 years. In symptomatic ones, surgery is indicated, aiming to drain the cyst content and safely remove as much of the capsule as possible. Following surgical intervention, headaches and visual field defects improve or resolve in a significant number of patients (40-100% and 33-100%, respectively) and partial hypopituitarism recovers in 14-50%. Data on relapse rates published in the last 15 years are based on variable follow-up periods and show wide variation (between 0% and 33%). The lowest relapse rates have been described in reports with relatively short mean observation periods (<3 years), whereas in those with longer follow-up the relapse rates increase. Most of the relapses occur within 5-6 years, suggesting that follow-up is required for at least 5 years after surgery. Risk factors for relapse include the presence of squamous metaplasia in the cyst wall, cyst size and the presence of inflammation. Long-term sufficiently powered studies aiming to clarify the natural history of asymptomatic RCCs and of those relapsing postoperatively are required

The outcome of macroprolactinomas resistant to dopamine agonists

Aim: The present study aims to assess the final outcome after combined therapeutic approaches in patients with macroprolactinoinas resistant to dopamine agonists (DA). Patients: Records of patients with macroprolactinoma hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005, were reviewed. There were 29 eligible patients resistant to DA therapy (8 men and 21 women), out of 119 patients with macroprolactinoinas; age at diagnosis ranged between 16-59 years. Methods: Rapid fluoroimmunoassay using Europium was used for hormonal levels; computed tomography imaging and/or MRI were used for tumor size. Study design: The resistance to DA drugs was evaluated using minimal criteria: the lack of prolactinoma response to current daily close of Bromocriptine (BRC) 7.5 mg/day or to Cabergoline (CAB) up to 2 mg/week for at least 6 months (step 1) or maximal criteria: the lack of response to high BRC doses (30 mg/day) or CAB doses between 2.5-4 mg/week for at least 6 months (step 2). The lack of response was considered if PRL levels remained above the upper normal limit (20 ng/mL) and the tumor mass size decreased with less than 50%. All resistant cases at step 1 received thereafter maximal medical therapy with DA drugs, according to step 2. Thereafter, resistant macroprolactinomas after step 2 were submitted to step 3 - high voltage radiotherapy ± surgery. Results: Outcome of medical therapy with DA (n=29): Overall, 7 resistant macroprolactinomas were solved by increasing BRC dose (n=5) or changing BRC to CAB (n=2). But 22/119 (18.5%) patients remained resistant to DA drugs independent of dose, duration or type of drug used. 14 patients failed to normalize PRL levels despite CAB treatment in doses up to 7 mg/week. Outcome of radiotherapy alone or combined with surgery (n=15): PRL normalization was achieved in 4 patients out of the only 7 assessed at least at 18 months after radiotherapy. Withdrawal of DA therapy revealed 2 cured cases, both after radiotherapy and surgery. Outcome of surgery: Only one patient normalized PRL levels after surgery, but she soon relapsed. Apparently, only one case of acquired resistance to DA drugs was revealed. Conclusion: The resistance was successfully over passed in 38% cases (11 out of 29). Adding these results to the low cure rate of DA responsive prolactinomas, proved by drug withdrawal, it is tempting to suggest that a selection of biological resistant cells is produced by the medical therapy in majority of macroprolactinomas**

The outcome of macroprolactinomas resistant to dopamine agonists

Aim: The present study aims to assess the final outcome after combined therapeutic approaches in patients with macroprolactinoinas resistant to dopamine agonists (DA). Patients: Records of patients with macroprolactinoma hospitalized in the Institute of Endocrinology, Bucharest, between 1978-2005, were reviewed. There were 29 eligible patients resistant to DA therapy (8 men and 21 women), out of 119 patients with macroprolactinoinas; age at diagnosis ranged between 16-59 years. Methods: Rapid fluoroimmunoassay using Europium was used for hormonal levels; computed tomography imaging and/or MRI were used for tumor size. Study design: The resistance to DA drugs was evaluated using minimal criteria: the lack of prolactinoma response to current daily close of Bromocriptine (BRC) 7.5 mg/day or to Cabergoline (CAB) up to 2 mg/week for at least 6 months (step 1) or maximal criteria: the lack of response to high BRC doses (30 mg/day) or CAB doses between 2.5-4 mg/week for at least 6 months (step 2). The lack of response was considered if PRL levels remained above the upper normal limit (20 ng/mL) and the tumor mass size decreased with less than 50%. All resistant cases at step 1 received thereafter maximal medical therapy with DA drugs, according to step 2. Thereafter, resistant macroprolactinomas after step 2 were submitted to step 3 - high voltage radiotherapy ± surgery. Results: Outcome of medical therapy with DA (n=29): Overall, 7 resistant macroprolactinomas were solved by increasing BRC dose (n=5) or changing BRC to CAB (n=2). But 22/119 (18.5%) patients remained resistant to DA drugs independent of dose, duration or type of drug used. 14 patients failed to normalize PRL levels despite CAB treatment in doses up to 7 mg/week. Outcome of radiotherapy alone or combined with surgery (n=15): PRL normalization was achieved in 4 patients out of the only 7 assessed at least at 18 months after radiotherapy. Withdrawal of DA therapy revealed 2 cured cases, both after radiotherapy and surgery. Outcome of surgery: Only one patient normalized PRL levels after surgery, but she soon relapsed. Apparently, only one case of acquired resistance to DA drugs was revealed. Conclusion: The resistance was successfully over passed in 38% cases (11 out of 29). Adding these results to the low cure rate of DA responsive prolactinomas, proved by drug withdrawal, it is tempting to suggest that a selection of biological resistant cells is produced by the medical therapy in majority of macroprolactinomas**

Do the limits of serum prolactin in disconnection hyperprolactinaemia need re-definition? A study of 226 patients with histologically verified non-functioning pituitary macroadenoma.

BACKGROUND: The differentiation of a pituitary non-functioning macroadenoma from a macroprolactinoma is important for planning appropriate therapy. Serum PRL levels have been suggested as a useful diagnostic indicator. However, values between 2500 and 8000 mU/l are a grey area and are currently associated with diagnostic uncertainty. OBJECTIVE: We wished therefore, to investigate the serum PRL values in a large series of patients presenting with apparently non-functioning pituitary macroadenomas. PATIENTS AND METHODS: All patients presenting to the Department of Endocrinology in Oxford with clinically non-functioning pituitary macroadenomas (later histologically verified) between 1990 and 2005 were studied. Information documented in the notes on the medications and on the presence of conditions capable of affecting the serum PRL levels at the time of blood sampling was also collected. RESULTS: Two hundred and twenty-six patients were identified (median age at diagnosis 55 years, range 18-88 years; 146 males/80 females; 143 gonadotroph, 46 null cell, 25 plurihormonal and 12 silent ACTH adenomas). All tumours had suprasellar extension. At the time of blood sampling 41 subjects were taking medications capable of increasing serum PRL. Hyperprolactinaemia was found in 38.5% (87/226) of the patients. The median serum PRL values in the total group were 386 mU/l (range 16-3257) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-3257) and in those not taking drugs capable of increasing serum PRL 363 mU/l (range 16-2565) (males: median 299 mU/l, range 16-1560; females: median 572 mU/l, range 20-2565). Serum PRL < 2000 mU/l was found in 98.7% (223/226) of the total group and in 99.5% (184/185) of those not taking drugs. Among the three subjects with serum PRL > 2000 mU/l, two were taking oestrogen preparations. CONCLUSIONS: Based on a large series of histologically confirmed cases, serum PRL > 2000 mU/l is almost never encountered in nonfunctioning pituitary macroadenomas. Values above this limit in the presence of a macroadenoma should not be surrounded by diagnostic uncertainty (after acromegaly or Cushing's disease have been excluded); a prolactinoma is the most likely diagnosis and a dopamine agonist should be considered as the treatment of choice

Outcome in surgically treated Rathke's cleft cysts: long-term monitoring needed.

OBJECTIVE: To clarify the outcome of all cases of Rathke's cleft cysts (RCC) treated surgically and followed up in Oxford during a long-term period. SUBJECTS AND METHODS: The records of all patients with RCC seen in the Department of Endocrinology between January 1978 and June 2009 were reviewed. RESULTS: A total of 33 patients (20 females, median age 43 years) were identified. At presentation, major visual field defects were detected in 58% of patients and gonadotrophin, ACTH and TSH deficiency in 60, 36 and 36% of patients respectively. Desmopressin treatment was required in 18% of patients. Treatment consisted of cyst evacuation combined with or without biopsy/removal of the wall. Post-operatively, visual fields improved in 83% of patients with impairment, whereas there was no reversal of ACTH or TSH deficiency or of diabetes insipidus. All but one subject had imaging follow-up during a mean period of 48 months (range 2-267). Cyst relapse was detected in 22% of patients at a mean interval of 29 months (range 3-48 months); in 57% of them, the recurrence was symptomatic. Relapse-free rates were 88% at 24-months and 52% at 48-months follow-up. At last assessment, at least quadrantanopia was reported in 19% of patients, gonadotrophin, ACTH and TSH deficiency in 50, 42 and 47% of patients respectively. Desmopressin treatment was required in 39% of patients. CONCLUSIONS: In this study of patients with RCC and long-term follow-up, we showed a considerable relapse rate necessitating long-term monitoring. Surgical intervention is of major importance for the restoration of visual field defects, but it does not improve endocrine morbidity, which in the long-term affects a substantial number of patients