Radiation techniques for acromegaly

Radiotherapy (RT) remains an effective treatment in patients with acromegaly refractory to medical and/or surgical interventions, with durable tumor control and biochemical remission; however, there are still concerns about delayed biochemical effect and potential late toxicity of radiation treatment, especially high rates of hypopituitarism. Stereotactic radiotherapy has been developed as a more accurate technique of irradiation with more precise tumour localization and consequently a reduction in the volume of normal tissue, particularly the brain, irradiated to high radiation doses. Radiation can be delivered in a single fraction by stereotactic radiosurgery (SRS) or as fractionated stereotactic radiotherapy (FSRT) in which smaller doses are delivered over 5-6 weeks in 25-30 treatments. A review of the recent literature suggests that pituitary irradiation is an effective treatment for acromegaly. Stereotactic techniques for GH-secreting pituitary tumors are discussed with the aim to define the efficacy and potential adverse effects of each of these techniques

Acromegaly

Acromegaly is an acquired disorder related to excessive production of growth hormone (GH) and characterized by progressive somatic disfigurement (mainly involving the face and extremities) and systemic manifestations. The prevalence is estimated at 1:140,000–250,000. It is most often diagnosed in middle-aged adults (average age 40 years, men and women equally affected). Due to insidious onset and slow progression, acromegaly is often diagnosed four to more than ten years after its onset. The main clinical features are broadened extremities (hands and feet), widened thickened and stubby fingers, and thickened soft tissue. The facial aspect is characteristic and includes a widened and thickened nose, prominent cheekbones, forehead bulges, thick lips and marked facial lines. The forehead and overlying skin is thickened, sometimes leading to frontal bossing. There is a tendency towards mandibular overgrowth with prognathism, maxillary widening, tooth separation and jaw malocclusion. The disease also has rheumatologic, cardiovascular, respiratory and metabolic consequences which determine its prognosis. In the majority of cases, acromegaly is related to a pituitary adenoma, either purely GH-secreting (60%) or mixed. In very rare cases, acromegaly is due to ectopic secretion of growth-hormone-releasing hormone (GHRH) responsible for pituitary hyperplasia. The clinical diagnosis is confirmed biochemically by an increased serum GH concentration following an oral glucose tolerance test (OGTT) and by detection of increased levels of insulin-like growth factor-I (IGF-I). Assessment of tumor volume and extension is based on imaging studies. Echocardiography and sleep apnea testing are used to determine the clinical impact of acromegaly. Treatment is aimed at correcting (or preventing) tumor compression by excising the disease-causing lesion, and at reducing GH and IGF-I levels to normal values. Transsphenoidal surgery is often the first-line treatment. When surgery fails to correct GH/IGF-I hypersecretion, medical treatment with somatostatin analogs and/or radiotherapy can be used. The GH antagonist (pegvisomant) is used in patients that are resistant to somatostatin analogs. Adequate hormonal disease control is achieved in most cases, allowing a life expectancy similar to that of the general population. However, even if patients are cured or well-controlled, sequelae (joint pain, deformities and altered quality of life) often remain

Evaluation of the adequacy of levothyroxine replacement therapy in patients with central hypothyroidism.

As there are few data on the evaluation of the adequacy of levothyroxine (L-T4) therapy in patients with central hypothyroidism (CH), a prospective study was performed to assess the accuracy of various parameters in the follow-up of 37 CH patients. Total and free thyroid hormones, TSH, and a series of clinical and biochemical indexes of peripheral thyroid hormone action have been evaluated off and on L-T4 therapy. Samples were taken before the daily administration of L-T4. In all patients off therapy, clinical hypothyroidism and low levels of free T4 (FT4) were observed, whereas values of FT3, total T4, and total T3 were below the normal range in 73%, 57%, and 19% of cases, respectively. Most of the indexes of thyroid hormone action were significantly modified after L-T4 withdrawal and exhibited significant correlation with free thyroid hormone levels. During L-T4 replacement therapy, 32 patients had circulating levels of FT4 and FT3 and indexes within the normal range with a mean L-T4 daily dose of 1.5 +/- 0.3 microg/kg BW. Despite normal serum FT4, 3 patients had borderline high values of FT3 and a clear elevation of serum-soluble interleukin-2 receptor concentrations, suggesting overtreatment. Low or borderline low FT4/FT3 levels indicated undertreatment in 2 patients. The clinical parameters lack the required specificity for the diagnosis or follow-up of CH patients. The L-T4 daily dose should be established, taking into account the weight, the age, and the presence of other hormone deficiencies or pharmacological treatment of CH patients. In conclusion, our results indicate that the diagnosis of CH is reached at best by measuring TSH and FT4 concentrations. In the evaluation of the adequacy of L-T4 replacement therapy, both FT4 and FT3 serum levels together with some biochemical indexes of thyroid hormone action are all necessary to a more accurate disclosure of over- or undertreated patients

Long-term follow-up results of postoperative radiation therapy for Cushing disease.

Abstract Objectives Radiotherapy is currently used in patients with residual or recurrent pituitary adenomas after surgery. However, there is little information of longterm outcome of patients with Cushing’s disease following radiotherapy. We assessed the long-term efficacy and toxicity of conventional radiotherapy in the control of Cushing’s disease after unsuccessful transsphenoidal surgery. Patients and Methods Forty patients with Cushing’s disease were treated with conventional external beam radiotherapy at our Institution between 1988 and 2002. The median age was 38. All patients received radiotherapy following unsuccessful surgery or at tumour recurrence to a dose of 45–50 Gy in 25–28 fractions. The persistence of active disease after surgery was diagnosed by the increased high plasma cortisol levels, high 24 h urinary cortisol levels and absence of cortisol suppression after administration of dexamethasone. Results The 5 and 10 year local tumour control was 93% and the 5 and 10 year survival was 97 and 95%. Normalization of plasma cortisol was seen in 28% of patients at 1 year, 73% at 3 years, 78% at 5 years and 84% at 10 years. The average timing to remission was 24 months. The most common side effect was hypopituitarism that increased progressively during the follow- up, being present in 62% and in 76% of patients at 5 and 10 years after RT. There were no other serious complications as radiation induced optic neuropathy or second tumours. Conclusion Radiotherapy is effective in the long-term tumour- and hormone hypersecretion control of ACTHsecreting pituitary adenomas, however with a high prevalence of hypopituitarism. At the moment, it remains an important treatment option after failure of surgery. Keywords Radiotherapy ACTH-secreting pituitary adenoma Cushing’s disease Hypopitu

GIANT PROLACTINOMAS PRESENTING AS SKULL BASE TUMORS

BACKGROUND: Prolactinomas invading the skull base are rare, and could easily be confused with skull base tumors of nonpituitary origin. CASE DESCRIPTION: We report a series of 4 cases of giant prolactinomas invading the skull base and presenting with atypical symptoms. Case 1 presented with a short history of headache and nasal obstruction. Case 2 presented with progressive hypoacusia, dizziness, and ophthalmoplegia. In Case 3, the patient developed rapid progressive visual failure and psychiatric symptoms. Case 4 presented with a 1-year history of headache and retrorbital pain. The diagnosis of prolactinoma was made on the basis of tumor immunohistochemistry and/or high plasma prolactin levels (range from 650-6,500 ng/mL). Medical treatment with the dopamine agonist cabergoline was given; it was effective in normalizing prolactin levels and inducing tumor shrinkage. CONCLUSION: Prolactin levels should be measured in all large skull base tumors involving the pituitary region before any surgery or inappropriate radiotherapy is performed