Endonasal transsphenoidal surgery and multimodality treatment for giant pituitary adenomas

Objective Giant pituitary adenomas (≥40 mm) pose a major management challenge. We describe the experience of a single surgeon and a dedicated neuro‐endocrine team with multimodality treatment of these tumours in three specialized institutions. Design Retrospective data set analyses. Patients Fifty‐one consecutive patients with a giant adenoma (39 endocrine‐inactive, 12 endocrine‐active; mean tumour diameter 45 mm) treated over 10 years by an endonasal transsphenoidal approach were included. All patients had surgical resection followed by radiotherapy and/or medical therapy as judged necessary. Measurements Hormonal and visual status, extent of resection, tumour control rates, complications and use of medical and radiotherapy were evaluated. Results Surgery resulted in gross total, near total and subtotal removal in21 (41%), 10 (20%) and 20 (39%) patients respectively. Complete tumour removal was associated with absence of cavernous sinus invasion (P < 0·001). Long‐term endocrine function improved in 49% of patients and new endocrinopathy occurred in 14·6%; 76% required long‐term hormone replacement therapy. Vision improved in 81·5% of the patients and there was no visual worsening. At the last follow up (median 30 months), tumour control was achieved in 96% of patients: 59% with surgery alone, 20% with surgery plus focussed radiotherapy, 18% with surgery and medical therapy and two with all three modalities. Conclusions Endonasal surgery provides effective initial treatment for patients with giant adenomas. Multimodality therapy was needed in almost 50% of patients and this rate will likely increase with longer follow up. Close collaboration of neurosurgeons with endocrinologists and radiation oncologists is essential for optimal treatment of patients with these challenging tumours.     

Elevated serum parathyroid hormone concentration in eucalcemic patients after parathyroidectomy for primary hyperparathyroidism and its relationship to vitamin D profile

Elevation of serum parathyroid hormone (PTH) level in eucalcemic patients after parathyroidectomy for primary hyperparathyroidism has been described in up to 40% of patients, but little is known about its etiology or clinical significance. To better understand the cause of this phenomenon, we studied 49 patients without renal dysfunction or osteomalacia who underwent parathyroidectomy for primary hyperparathyroidism. Patients were categorized into 2 groups based on their serum PTH and calcium levels after parathyroidectomy: (1) elevated PTH with eucalcemia (n = 21), (2) normal PTH with eucalcemia (n = 28). Elevation of serum PTH with eucalcemia after parathyroidectomy occurred in 43% of patients. Patients in group 1 had significantly higher preoperative and postoperative mean serum PTH levels and significantly lower postoperative serum levels of 1,25(OH)(2)D(3), 1,25(OH)(2)D(3)/25(OH)D(3) ratio, and 1,25(OH)(2)D(3)/PTH ratio compared with patients in group 2. Serum PTH in group 1 patients normalized as early as 3 months, but remained elevated in some patients for more than 4 years, and was not associated with development of recurrent hypercalcemia. Normalization of serum PTH in group 1 patients was associated with significant increase in 1,25(OH)(2)D(3) and 1,25(OH)(2)D(3)/PTH ratio. Our data suggest that elevation of serum PTH in eucalcemic patients after parathyroidectomy is a frequently reversible state of resistance of the kidneys to PTH-mediated 1-alpha hydroxylation of 25(OH)D(3) and does not signify subsequent recurrence of hyperparathyroidism.     

Pregnancy-associated Cushing’s disease? An exploratory retrospective study

Purpose

In most clinical series of Cushing’s disease (CD), over 80% of patients are women, many of whom are of reproductive age. The year following pregnancy may be a common time to develop CD. We sought to establish the incidence of CD onset associated with pregnancy.

Methods

A retrospective review was conducted for patients with biochemically-proven CD. Demographics, clinical history, biochemistry, imaging, pathology, and outcomes were reviewed. Pregnancy-associated CD was defined as symptom onset within 1 year of childbirth.

Results

Over 10 years, 77 patients including 64 women (84%), with CD underwent endonasal surgery. Of the 64 women, 64% were of reproductive age (15–45 years) at the time of diagnosis, and 11 (27%) met criteria for pregnancy-associated CD. Of these 11 women, median number of pregnancies prior to onset of CD was 2 (range 1–4) compared to zero (range 0–7) for 30 other women with CD onset during reproductive age (p?=?0.0024). With an average follow-up of 47?±?34 months, sustained surgical remission rates for woman with pregnancy-associated CD, other women of reproductive age, and women not of reproductive age were 91%, 80% and 83%, respectively. The average lag-time from symptom onset to diagnosis for women with pregnancy-associated CD was 4?±?2 years.

Conclusions

In this exploratory study, over one quarter of women of reproductive age with CD appeared to have symptomatic disease onset within 1 year of childbirth. This relatively high rate of pregnancy-associated CD suggests a possible causal relationship related to the stress of pregnancy and pituitary corticotroph hyperactivity in the peripartum period. This possible association suggests a heightened degree of clinical suspicion and biochemical testing for CD may be warranted after childbirth. Further study of this possible link between pregnancy and CD is warranted.

     

Complication avoidance protocols in endoscopic pituitary adenoma surgery: a retrospective cohort study in 514 patients

Pituitary - To evaluate the impact of using consistent complication-avoidance protocols in patients undergoing endoscopic pituitary adenoma surgery including techniques for avoiding anosmia,...     

Transit dosimetry in dynamic IMRT with an a-Si EPID

Using an amorphous silicon (a-Si) EPID for transit dosimetry requires detailed characterization of its dosimetric response in a variety of conditions. In this study, a measurement-based model was developed to calibrate an a-Si EPID response to dose for transit dosimetry by comparison with a reference ionization chamber. The ionization chamber reference depth and the required additional buildup thickness for electronic portal imaging devices (EPID) transit dosimetry were determined. The combined effects of changes in radiation field size, phantom thickness, and the off-axis distance on EPID transit dosimetry were characterized. The effect of scattered radiation on out-of-field response was investigated for different field sizes and phantom thicknesses by evaluation of the differences in image profiles and in-water measured profiles. An algorithm was developed to automatically apply these corrections to EPID images based on the user-specified field size and phantom thickness. The average phantom thickness and an effective field size were used for IMRT fields, and images were acquired in cine mode in the presence of an anthropomorphic phantom. The effective field size was defined as the percentage of the jaw-defined field that was involved during the delivery. Nine head and neck dynamic IMRT fields were tested by comparison with a MatriXX two-dimensional array dosimeter using the Gamma (3 %, 3 mm) evaluation. A depth of 1.5 cm was selected as the ionization chamber reference depth. An additional 2.2 mm of copper buildup was added to the EPID. Comparison of EPID and MatriXX dose images for the tested fields showed that using a 10 % threshold, the average number of points with Gamma index <1 was 96.5 %. The agreement in the out-of field area was shown by selection of a 2 % threshold which on average resulted in 94.8 % of points with a Gamma index <1. The suggested method is less complicated than previously reported techniques and can be used for all a-Si EPIDs regardless of the manufacturer.