Pituitary Irradiation Research Articles

Chapter 22 - Nelson syndrome: definition and management

Nelson syndrome is an important complication of treatment with total bilateral adrenalectomy (TBA) for patients with refractory Cushing's disease. Although early cases of Nelson syndrome often presented with the clinical features of large sellar masses, the modern face of Nelson syndrome has changed primarily due to earlier detection (with highly resolved magnetic resonance imaging (MRI) and sensitive ACTH assays) and greater awareness of the condition, resulting in reduced morbidity and mortality. Although lack of administration of neoadjuvant pituitary radiotherapy post-TBA surgery may predict future development of Nelson syndrome, other predictive factors remain controversial. Therefore, Nelson syndrome should be screened for closely and long-term in all patients with a history of Cushing's disease and TBA. The diagnosis of Nelson syndrome remains controversial, and the pathogenesis of this condition is incompletely understood. Current hypotheses include the "released negative feedback" mechansism (residual pituitary corticotropinoma cells are "released" from the negative feedback effects of cortisol following TBA), and the "aggressive corticotropinoma" mechanism (Nelson syndrome is most likely to develop in those patients with refractory treatments - including TBA - for an underlying aggressive corticotropinoma). Effective management of Nelson syndrome with pituitary surgery and radiotherapy is often a challenge. Other therapies (such as Gamma Knife surgery and temozolomide) play an important role and merit further research into their efficacy and placement in the management pathway of Nelson syndrome.

Cushing’s disease: current trends in treatment

SUMMARY Cushing’s disease (CD) is an uncommon endocrine disorder resulting from an adrenocorticotrophin-producing pituitary adenoma. Its clinical features and subsequent comorbidities are the consequence of hypercortisolism and may be life-threatening if untreated. Trans-sphenoidal selective adenomectomy or hypophysectomy remain recommended first-line treatments for CD and may be repeated if unsuccessful or following recurrence of the tumor. Pituitary radiotherapy, either conventional fractionated external beam or in the form of radiosurgery, is a second-line treatment option, but its effects are delayed for several years. Bilateral adrenalectomy is a valuable treatment option for acutely unwell patients or for those who are unable to take or tolerate medical therapy. Steroidogenesis inhibitors such as metyrapone, ketoconazole, etomidate and mitotane have their place at many stages in the management of CD and are usually very effective. Pituitary tumor-targeted agents, such as cabergoline or pasireotide, ...

Baseline characteristics and effects of ten years of growth hormone (GH) replacement therapy in adults previously treated with pituitary irradiation

ContextLittle is known of the importance of previous irradiation therapy for baseline characteristics and responsiveness to GH replacement in GH deficient (GHD) adults. Objective/design/patientsIn this prospective, single-centre, open-label study, the effects of 10-year GH replacement were determined in 18 GHD adults that had previously received conventional external fractionated pituitary irradiation therapy (IRR group) and 18 non-irradiated GHD patients (non-IRR group). All patients had adult onset disease and complete deficiency of anterior pituitary hormones and both groups were comparable in terms of age, gender, body mass index (BMI), and waist:hip ratio. ResultsAt baseline, IRR patients had higher serum triglyceride (TG) and insulin levels and lower high density lipoprotein (HDL)-cholesterol (HDL-C) level than non-IRR patients (all p<0.05). The 10-year GH replacement improved body composition, bone mass and serum lipid profile without any between-group differences, except for a marginally more beneficial response in serum TG level in the IRR patients. After 10years, there was no between-group difference in any variable after correction for a higher replacement dose of glucocorticoids in the IRR patients at study end using an analysis of covariance. During the 10-year GH replacement, 5 IRR patients suffered from vascular events (2 fatal) whereas only one non-fatal vascular event occurred in the non-IRR patients. ConclusionsIRR patients with GHD display a more severely impaired cardiovascular risk profile at baseline, which was reversed by the 10-year GH replacement after correction for the higher glucocorticoid dose at study end. However, vascular events occurred more frequently in the IRR patients.

Radioterapia nos tumores da hipófise – atualizações e controvérsias

IntroductionRadiotherapy is an effective treatment for residual or recurrent pituitary tumors with tumor volume control and decrease or normalization of excess hormone secretion in the clinically functioning adenomas. The risks of long-term toxicity, being the hypopituitarism the most frequent, make radiation therapy a rarely used second-line treatment. ObjectivesTo describe efficacy, safety and role of conventional external beam radiotherapy, as well as radiosurgery in the treatment of pituitary tumors. Material and MethodsSearch of original or review papers published until January 2012 with the following keywords“pituitary radiotherapy”, “radiotherapy for pituitary adenomas”, “stereotactic radiotherapy”, “pituitary radiosurgery”, “radiation therapy”, “radiotherapy for Cushing's Disease”, “radiotherapy for acromegaly”, “radiotherapy for non-functioning pituitary adenomas”, “radiotherapy for prolactin-secreting pituitary tumors”. ConclusionsRadiotherapy still has a complementary role to surgical resection, although it could be appropriate as a first-line treatment in selected cases. The new modalities of radiation treatment show promising results in the reduction of toxicity as well as in the latency of hormonal response; however more studies are necessary to prove long-term efficacy and safety.

Adenomas of the pituitary gland and postoperative 3D conformal external beam radiation therapy

Aim-Background Adenomas of the pituitary gland are defined as microadenomas or macroadenomas. The main symptoms are hormonal dysfunctions, visual dysfunctions and headache. Treatment modalities include medical management, surgery and external beam radiotherapy (3D EBRT). The risk of recurrence is higher when surgery is not followed by postoperative radiation therapy.

Pituitary apoplexy in T3 thyrotoxicosis

A 58-year-old male was brought to our emergency department because of acute onset of visual disturbances and headache. His past medical history revealed no specific illness. He was a nonsmoker. On history taking, we learned that the patient had experienced weight loss with decreased sexual activity for several months. On physical examination, beard and axillary hair were decreased. The thyroid gland was mildly enlarged on palpation. Examination of vital signs revealed a blood pressure of 120/60 mmHg, heart rate of 80/min, respiration rate of 18 breaths/min, and body temperature of 36.5 C. Radiologic examinations with brain computed tomography (CT) showed a mass in the pituitary gland. Laboratory tests revealed as follows: a serum sodium of 134 (135–150) mmol/L, serum glucose of 6.6 mmol/L, FSH of 0.9 (1.4–18.1) IU/L, LH of \0.07 (1.5–9.3) IU/L, testosterone of\0.01 (0.09–0.37) nmol/L, prolactin of 456.5 (78.3–691.3) pmol/L, IGF-1 of 9.0 (9.3–38.0) nmol/L, free T4 of 19.10 (11.5–22.7) pmol/L, TSH of \0.01 (0.55–4.78) mIU/L, and ACTH of 5.87 pmol/L. The random cortisol level was not measured before hydrocortisone was administered. Sellar magnetic resonance imaging (MRI) showed a 27 9 35 9 24 mm pituitary mass that was bulging into suprasellar area and contained a fluid–fluid level (Fig. 1a). Pituitary macroadenoma with hemorrhage was highly suspected. Standard ophthalmologic examination showed bilateral hemianopsia. Therefore, a high dose of hydrocortisone was administered intravenously immediately. However, neurosurgery was performed on this patient because of persistence of the visual field defect despite steroid treatment. Endonasal transsphenoidal surgery for pituitary adenoma was performed. The final pathologic diagnosis was pituitary adenoma originating from a gonadotrope. On the other hand, a diffuse goiter was detected on palpation and the free T4 level was in the high range of normal as described earlier. Therefore, we measured the free T3 level and thyroid autoantibody. Results revealed a free T3 of 9.7 (3.1–6.8) pmol/L, anti-TPO antibody of 600 (*34) IU/mL, and anti-TSH receptor antibody of 33.82 (*1.75) IU/L. Thyroid scan with pertechnetate revealed a diffuse toxic goiter that was compatible with primary hyperthyroidism (Fig. 1b). Therefore, antithyroid drug was started with physiologic replacement of hydrocortisone. Pituitary apoplexy is a life-threatening clinical syndrome characterized by sudden onset of headache, and visual impairment caused by the rapid enlargement of the pituitary adenoma usually due to hemorrhage. Various predisposing factors of pituitary apoplexy, such as systemic hypertension, alteration of intracranial pressure gradients, head trauma, pituitary irradiation, pregnancy, cerebral angiography, anticoagulation, dynamic study of pituitary gland, hemodialysis, and surgeries including cardiac surgery, have been reported. Among these factors, hypertension was the most common predisposing factor. It is also well known that thyroid dysfunction results in changes in cardiac output, cardiac contractility, blood pressure, vascular resistance, and rhythm disturbances [1]. Therefore, theoretically, it is possible that primary thyroid dysfunction causes pituitary apoplexy in patients with pituitary adenoma. However, clinically, the association between pituitary apoplexy and thyroid dysfunction has been unclear, and only one case of pituitary apoplexy caused by primary K. A. Lee T. S. Park H. S. Baek H. Y. Jin (&) Division of Endocrinology and Metabolism, Department of Internal Medicine, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Chonbuk National University, Geonji Road #20, Deokjin-gu, Jeonju 561-712, South Korea e-mail: mdjinhy@jbnu.ac.kr

Metastatic ACTH-producing pituitary carcinoma managed with combination pasireotide and bevacizumab following failure of temozolamide therapy: A case report.

e13022 Background: ACTH-producing pituitary carcinomas (APPC) are malignant neuroendocrine tumors affecting the adenohypophysis. They are extremely rare, with a poor prognosis. They are poorly responsive to chemotherapy and radiotherapy. We report the case of a 25 year old female with a diagnosis of APPC, metastatic to bone, treated with temozolamide, followed by bevacizumab and the novel agent, pasireotide. Methods: The patient was diagnosed in 2002 with an ACTH-secreting pituitary macroadenoma causing Cushing’s disease. Despite two transphenoidal surgeries, bilateral adrenalectomies, craniotomy with excision of pituitary fossa tumour and radiotherapy she developed aggressive Nelson’s Syndrome. Following discontinuation of a somatostatin analogue in 2009 her ACTH levels rose dramatically causing progressive skin hyperpigmentation. Her disease continued to progress despite CyberKnife treatment. She was referred for temozolamide chemotherapy for treatment of the pituitary adenoma. At review, she had severe back pain. Investigations suggested metastatic disease and biopsy confirmed a diagnosis of metastatic APPC to bone.We commenced treatment with Temozolamide, however her disease progressed – ACTH levels were &gt;200,000pmol/l in June 2012. Molecular profiling completed on the patient’s tissue was negative. Pasireotide, a novel multi-somatostatin receptor analogue, was commenced concomitantly with the anti-angiogenesis agent bevacizumab. Results: Treatment response is being assessed with imaging, serial monitoring of serum ACTH levels and skin examination. Interval imaging has shown stable disease, ACTH levels have decreased to 113,000pg/ml. Conclusions: Pituitary carcinomas are extremely rare representing 0.1-0.2% of pituitary neoplasms. To date, there is no established standard treatment, although there are reports of response to temozolamide.Our patient exhibited a clinical improvement and a reduction in ACTH levels after 6 months of combination therapy with pasireotide and bevacizumab. This combination is a possible therapeutic option in patients with metastatic ACTH-producing pituitary carcinoma.

Gonadotoxicité des traitements anti-cancéreux chez l’enfant

Numerous cytotoxic drugs used to treat childhood cancers, as well as pelvic or hypothalamo- pituitary irradiation and gonadal surgery, can affect subsequent hormonal function and fertility. Prevention of these adverse consequences is based primarily on therapeutic de-escalation when possible, and now also on gonad or gamete preservation. These patients and their parents must receive thorough information, taking into account the child's age, the proposed treatments, and the length of follow-up. Teams treating childhood cancers must receive appropriate training, and access to innovative fertility-preserving techniques must be guaranteed at the national level.

Approach to the Cushing's Disease Patient With Persistent/Recurrent Hypercortisolism After Pituitary Surgery

Although it is the ideal treatment, pituitary surgery is not always successful, and success is not always lasting. Close surveillance, clinical and biological, will detect immediate failure or late recurrence. The reason must be thoroughly explored with the somewhat dogmatic rule that the patient should be offered the best surgery in expert hands, and a repeat surgical attempt must be systematically discussed. When repeat pituitary surgery is not indicated or has failed, then comes the difficult task to choose between a number of options directed toward different targets: directly suppress tumor ACTH by pituitary radiotherapy (conventional or stereotaxic) or with medications (somatostatin analog such as pasireotide, or dopaminergic drug such as cabergoline), directly suppress adrenocortical activity with medications (inhibitors of adrenal steroidogenesis such as ketoconazole or metyrapone, or the adrenolytic Lysodren), or by surgery (bilateral adrenalectomy), and finally oppose peripheral cortisol action with the antiglucocorticoid mifepristone. No single option is ideal, able to provide at the same time a high success rate and a rapid onset of action, to restore a normal pituitary adrenal axis, and to have good tolerability. Close follow-up and thorough evaluation of the cortisolic status will eventually dictate a switch in treatment options and/or combination strategies over time. The tumor status and its possible oncogenic threat, the severity of the hypercortisolism, and the patient perspectives (wish of fertility) are among the major parameters that can help a multidisciplinary approach toward the best option.

Visual Diagnosis: Obese 11-month-old Female With Round Facies

1. Nancy L. Beck, MD* 2. Alba E. Morales, MD† 3. R.F. Buchmann, DO‡ 4. R.J. Birusingh, DO§ 1. *Assistant Professor, Division of Endocrinology, Department of Pediatrics, Texas Tech University Health Sciences Center, Lubbock, TX. 2. †Associate Professor, Division of Diabetes and Endocrine, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR. 3. ‡Assistant Professor, Radiology and Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR. 4. §Assistant Professor, Pediatric Pathology, University of Arkansas for Medical Sciences, Little Rock, AR. An 11-month-old girl presents to the clinic for a mild respiratory illness. Her parents also voice concern about their daughter’s appearance and offer a photograph of her taken at age 9 months (Fig 1). Both parents are slim and healthy. Figure 1. The patient at age 9 months. On examination, the infant is noted to have a round face, generalized fine body hair, acne, and central obesity (Fig 2). She currently weighs 9.6 kg (50th percentile for age), her length is 69 cm (10th percentile), and her head circumference is 43 cm (10th percentile). She was born by uncomplicated vaginal delivery having a birthweight of 3.125 kg (25th percentile) and a length of 48 cm (75th percentile). Review of the girl’s growth curves reveals the absence of linear growth during the previous month (Fig 3). Figure 2. The patient at age 11 months. Figure 3. Growth chart reveals cessation of linear growth. The child’s vital signs are normal for her age. She has mild nasal congestion. Her genitalia appear normal, but her neurologic examination shows delayed gross motor skills. She is able to pull to stand but does not cruise or walk. Based on a suspected diagnosis, the patient undergoes several laboratory examinations. Midnight salivary cortisol levels were 29.2 nmol/L (reference <0.3–4.3) and 33.4 nmol/L on consecutive nights. An overnight dexamethasone (0.3 mg/m2) suppression test revealed an 8 am serum cortisol level of 25.4 μg/dL (701 nmol/L) (reference <3 μg/dL or 83 nmol/L). The plasma cortisol concentration at 4 pm was 29.4 μg/dL (811 nmol/L). The results of renal and thyroid function tests were normal. Serum corticotropin levels obtained on two occasions were …

Encouraging efficacy of modern conformal fractionated radiotherapy in patients with uncured Cushing’s disease

The objective of this study was to assess the efficacy of modern conformal fractionated radiotherapy (RT) in patients with uncured Cushing's disease (CD) after failed transsphenoidal surgery (TSS). In this retrospective analysis, we reviewed records of patients with CD who received modern conformal fractionated RT between 2001 and 2010. Records were evaluated for frequency and interval of remission post RT. The change in the tumour size, endocrine insufficiencies and complications developing post RT were noted. Remission was defined as 2mg Low dose dexamethasone suppressed cortisol of <50nmol/l. During the study period of 10years, a total of 24 patients (mean age: 27.9, range: 21-48years) underwent pituitary RT for CD. Out of these, long term follow up was available for 22 patients and 20 patients (15F/5M, 12 microadenomas/8 macroadenomas) were included for final analysis. All the patients received modern conformal fractionated external beam RT (45Gy in 25 fractions) with the median follow up of 37.5months (range 12-144). Fifteen patients (10 microadenomas/5 macroadenomas) underwent remission after a median follow up period of 20months. None of the patients had recurrence. Post RT, new onset endocrine deficiencies were seen in 8 (40%) patients. Modern conformal fractionated external beam radiotherapy is an effective modality for treatment of adult patients with CD after failed TSS.

Chemotherapy-Induced Regression of an Adrenocorticotropin-Secreting Pituitary Carcinoma Accompanied by Secondary Adrenal Insufficiency

Purpose. Adrenocorticotropin- (ACTH-) secreting pituitary carcinomas are rare and require multimodality treatment. The aim of this study was to report the response to various therapies and discuss the potential development of secondary adrenal insufficiency with cytotoxic chemotherapy. Methods. This report describes a man with a large silent corticotroph adenoma progressing to endogenous hypercortisolism and metastatic ACTH-secreting pituitary carcinoma over a period of 14 years. Results. Seven years after initial presentation, progressive tumor enlargement associated with the development of hypercortisolism mandated multiple pituitary tumor debulking procedures and radiotherapy. Testing of the Ki-67 proliferation index was markedly high and he developed a hepatic metastasis. Combination therapy with cisplatin and etoposide resulted in a substantial reduction in tumor size, near-complete regression of his liver metastasis, and dramatic decrease in ACTH secretion. This unexpectedly resulted in symptomatic secondary adrenal insufficiency. Conclusions. This is the first reported case of secondary adrenal insufficiency after use of cytotoxic chemotherapy for metastatic ACTH-secreting pituitary carcinoma. High proliferative indices may be predictive of dramatic responses to chemotherapy. Given the potential for such responses, the development of secondary adrenal insufficiency may occur and patients should be monitored accordingly.

Low-dose Conformal Radiation Therapy for Ipilimumab-induced Hypophysitis

Purpose/Objective(s): Ipilimumab is an immunostimulatory anti-CTLA 4 antibody that has been shown to improve survival in patients with metastatic melanoma. Unfortunately, 10-15% of patients treated with ipilimumab develop hypophysitis, which is often treated with systemic steroids or ipilimumab cessation or dose reduction. As these treatments are not optimal for patients who may be responding to ipilimumab, we present here our initial experience treating ipilimumab-induced hypophysitis with low-dose conformal radiation therapy. Materials/Methods: This is a single institution retrospective review of metastatic melanoma patients with ipilimumab-induced hypophysitis who were treated with low-dose pituitary radiation therapy. All patients had biochemical evidence of pituitary dysfunction and MRI features of hypophysitis, including diffuse pituitary enlargement and enhancement. Radiation therapy was linear accelerator-based and consisted of three daily 150 cGy fractions delivered using 6or 15-MV photons. The PTV consisted of the pituitary gland and a 0.5-1 cm margin, which was treated via a three or five field conformal plan. A thermoplastic mask was employed for immobilization. Clinical follow-up as well as preand post-treatment MRIs were used to evaluate treatment efficacy, with pituitary volumes calculated using the volumetric formula for an ellipsoid (4/3 x p x R1 x R2 x R3). Mean preand post-radiation therapy pituitary volumes were compared using the Student’s t-test. Results: Between September 10, 2010 and February 24, 2012, seven patients (3 women, 4 men) with a median age of 65 years (range, 39-88) were treated. At a median follow-up of 31 weeks (range, 1-77), no patients experienced acute radiation therapy toxicity or developed new symptoms following treatment. Mean preand post-radiation therapy pituitary volumes were 796.7 (range, 433.1-962.5) and 380.8 (range, 266.8-569.7) mm, respectively (p Z 0.005). Radiation therapy was delivered over a median of 5 days (range, 3-5) and without interruption in any patient. All patients who presented with generalized symptoms of fatigue, anorexia, and headache reported symptomatic improvement following treatment. Every patient who presented with a hormonal deficiency had persistent endocrine dysfunction at last follow-up. Conclusion: Low-dose conformal radiation therapy results in significant clinical improvement and radiographic response in patients with ipilimumab-induced hypophysitis, although there is no amelioration of endocrine dysfunction following treatment. This treatment represents a promising therapeutic option for patients with ipilimumab-induced hypophysitis whose survival may be adversely affected by treatment with systemic steroids or interference of ipilimumab administration. Additional exploration and follow-up is necessary to determine whether early treatment initiation can reverse endocrine dysfunction. Author Disclosure: P.L. Menzel: None. A. Geng: None. C. Marquez: None. M. Scala: None. D. Minor: None. R. Abendroth: None.

Thyrotropin-secreting pituitary adenomas: diagnosis and management of patients from one Chinese center

Thyrotropin-secreting pituitary adenoma (TSHoma) is rare and it is also a rare cause of thyrotoxicosis. Failure to detect the presence of TSHoma may result in dramatic consequences. This study is a review of our experience in the management of TSHoma at Huashan Hospital, China. We followed up eight patients with TSHoma (five males and three females) between 2006 and 2011. The patients' medical records were retrieved, and the demographic data, clinical presentation and management, final outcomes and follow-up were reviewed, and surgery performed. All the eight patients had unsuppressed TSH levels with elevated thyroid hormone levels; and neuroimaging revealed pituitary lesions. Five patients (62.5%) were previously misdiagnosed as primary hyperthyroidism. They received pituitary adenomectomy, somatostatin analogs, and/or radiotherapy after definitive diagnosis. Serum TSH and thyroid hormone levels of all the patients restored to the normal levels during the follow-up. Adenomectomy is not curative in many TSHoma patients, it should be adjuvantly treated by pharmacological and/or radiotherapy, frequently. A combination of adenomectomy, somatostatin analogs, and radiotherapy is often required for long-term management of the disease.

Primary empty sella (PES): a review of 175 cases

The term primary empty sella (PES) makes reference to the herniation of the subarachnoid space within the sella turcica in patients with no history of pituitary tumor, surgery or radiotherapy. To retrospectively assess clinical features, radiological findings and the biochemical endocrine function from the records of 175 patients with a diagnosis of PES. One hundred seventy-five patients (150 females) were studied. The mean age at diagnosis was 48.2±14year. Most diagnoses were made by magnetic resonance imaging (n=172). In most patients, the pituitary function was assessed by basal pituitary hormones measurements. Pituitary scans were ordered for different reasons: headache (33.1%), endocrine disorders (30.6%), neurological symptoms (12.5%), visual disturbances (8.75%), abnormalities on sella turcica radiograph (8.75%) and others (6.25%). Multiple pregnancies were observed in 58.3% of women; headaches, obesity, and hypertension were found in 59.4, 49.5, and 27.3% of the studied population, respectively. Mild hyperprolactinemia (<50ng/ml) was present in 11.6% of women and 17.3% of men. Twenty-eight percent of our patients had some degree of hypopituitarism. In the male population, hypopituitarism represented 64% of cases, whereas it accounted for 22% of all females. PES seems to be more commonly found in middle-aged women, with a history of multiple pregnancies. In most patients, PES was discovered as an incidental finding on imaging studies, while in almost a quarter of patients PES was found during the diagnostic evaluation of anterior pituitary deficiency, which was more common in men.

Somatostatin analogs as a first-line treatment in acromegaly

To discuss the role of medical therapy of acromegaly as a first-line treatment, focusing on recent data on the use of somatostatin analogs (SSAs), the first-choice pharmacotherapy for treating acromegaly. Despite pituitary surgery and radiotherapy, a significant number of patients with acromegaly needed adjuvant medical therapy, and primary medical therapy nowadays is increasingly considered. According to a recent consensus statement on the management of acromegaly, primary pharmacological therapy with SSAs may be indicated in patients who are otherwise poor surgical candidates or refuse surgery, and in those in whom there is a low probability of a surgical cure. The long-acting SSAs have been found to be effective in improving symptoms and signs of acromegaly in a high percentage of patients and induce normalization of growth hormone and insulin-like growth factor-I levels approximately in 60-80% of patients, respectively. Evidence has suggested that SSAs induce a clinically significant tumor shrinkage when given as first-line, when this reduction of tumor volume could be helpful in improving the outcome of subsequent surgery or improving the clinical syndrome in patients with unacceptable surgical risk, whereas the tumor shrinkage was seen less frequently when the drug was used after surgical resection and/or radiotherapy. Pharmacological management plays a pivotal role in the treatment of acromegaly, and first-line medical therapy with SSAs is being widely used in clinical practice, either prior to surgery or in patients who are otherwise poor surgical candidates and in those in whom there is a low probability of a surgical cure.

Acromegaly

British Journal of Hospital MedicineVol. 73, No. Sup8 What you Need to Know AboutAcromegalyAhmed Yousseif, Efthimia Karra, Stephanie E BaldewegAhmed YousseifSearch for more papers by this author, Efthimia KarraSearch for more papers by this author, Stephanie E BaldewegSearch for more papers by this authorAhmed Yousseif; Efthimia Karra; Stephanie E BaldewegPublished Online:16 Aug 2013https://doi.org/10.12968/hmed.2012.73.Sup8.C119AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Ahmed S, Elsheikh M, Stratton IM, Page RC, Adams CB, Wass JA (1999) Outcome of transphenoidal surgery for acromegaly and its relationship to surgical experience. Clin Endocrinol (Oxf) 50: 561–7 Crossref, Medline, Google Scholar Biermasz NR, Pereira AM, Smit JW, Romijn JA, Roelfsema F (2005) Morbidity after long-term remission for acromegaly: persisting joint-related complaints cause reduced quality of life. J Clin Endocrinol Metab 90: 2731–9 Crossref, Medline, Google Scholar Colao A, Pivonello R, Auriemma RS et al. (2006) Predictors of tumor shrinkage after primary therapy with somatostatin analogs in acromegaly: a prospective study in 99 patients. J Clin Endocrinol Metab 91: 2112–18 Crossref, Medline, Google Scholar Drange MR, Fram NR, Herman-Bonert V, Melmed S (2000) Pituitary tumor registry: a novel clinical resource. J Clin Endocrinol Metab 85: 168–74 Medline, Google Scholar Giustina A, Barkan A, Casanueva FF et al. (2000) Criteria for cure of acromegaly: a consensus statement. J Clin Endocrinol Metab 85: 526–9 Medline, Google Scholar Holdaway IM, Rajasoorya C (1999) Epidemiology of acromegaly. Pituitary 2: 29–41 Crossref, Medline, Google Scholar Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89: 667–74 Crossref, Medline, Google Scholar Iranmanesh A, Grisso B, Veldhuis JD (1994) Low basal and persistent pulsatile growth hormone secretion are revealed in normal and hyposomatotropic men studied with a new ultrasensitive chemiluminescence assay. J Clin Endocrinol Metab 78: 526–35 Medline, Google Scholar Jenkins PJ, Bates P, Carson MN, Stewart PM, Wass JA (2006) Conventional pituitary irradiation is effective in lowering serum growth hormone and insulin-like growth factor-I in patients with acromegaly. J Clin Endocrinol Metab 91: 1239–45 Crossref, Medline, Google Scholar Lieberman SA, Bjorkengren AG, Hoffman AR (1992) Rheumatologic and skeletal changes in acromegaly. Endocrinol Metab Clin North Am 21: 615–31 Medline, Google Scholar Manjila S, Wu OC, Khan FR, Khan MM, Arafah BM, Selman WR (2010) Pharmacological management of acromegaly: a current perspective. Neurosurg Focus 29: E14 Crossref, Medline, Google Scholar Melmed S (2006) Medical progress: acromegaly. N Engl J Med 355: 2558–73 Crossref, Medline, Google Scholar Minniti G, Traish D, Ashley S, Gonsalves A, Brada M (2005) Risk of second brain tumor after conservative surgery and radiotherapy for pituitary adenoma: update after an additional 10 years. J Clin Endocrinol Metab 90: 800–4 Crossref, Medline, Google Scholar Murray RD, Melmed S (2008) A critical analysis of clinically available somatostatin analog formulations for therapy of acromegaly. J Clin Endocrinol Metab 93: 2957–68 Crossref, Medline, Google Scholar Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK (1994) Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol (Oxf) 41: 95–102 Crossref, Medline, Google Scholar Reddy R, Hope S, Wass J (2010) Acromegaly. BMJ 341: C4189 Crossref, Medline, Google Scholar Renehan AG, Shalet SM (2002) Acromegaly and colorectal cancer: risk assessment should be based on population-based studies. J Clin Endocrinol Metab 87: 1909 Medline, Google Scholar Rosenow F, Reuter S, Deuss U, Szelies B, Hilgers RD, Winkelmann W, Heiss WD (1996) Sleep apnoea in treated acromegaly: relative frequency and predisposing factors. Clin Endocrinol (Oxf) 45: 563–9 Crossref, Medline, Google Scholar FiguresReferencesRelatedDetails 1 August 2012Volume 73Issue Sup8ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 16 August 2013 Published in print 1 August 2012 Information© MA Healthcare LimitedPDF download

Traitement de la maladie de Cushing : progrès récents

Transsphenoidal surgery, possibly through the endoscopic approach, remains the first line treatment. Opposing cortisol action with mifepristone proved efficacious in some individual cases but but with major monitoring difficulties. Combined treatment with three anticortisolic drugs (metyrapone, ketokonazole, O,p’DDD) is particularly attractive in severe cases. The Nelson's syndrome has been revisited, and the corticotroph tumor progression should rather be cautiously assessed after bilateral adrenalectomy. Two molecules potentially act directly to suppress the ACTH secretion by the corticotroph adenoma: agonists of the D2 Dopamine receptor and of the somatostatin receptor type 5. Their efficacy remains modest (20 to 30% of the patients actually normalize urinary cortisol). Pituitary radiotherapy can be efficiently performed by stereotaxic approach.

Age at Menarche in Childhood Cancer Survivors: Results of a Nationwide Survey in Germany

Background/Aims: With rising cure rates of childhood cancer, side effects of treatment are attracting increasing interest. The present analysis evaluates the influence of tumor localization, radiotherapy and chemotherapy on the age of menarche. Methods: 4,689 former pediatric oncology patients, diagnosed 1980–2004, were contacted in collaboration with the German Childhood Cancer Registry. Results: 1,036 out of 1,461 female participants reported their age at menarche and had an oncological diagnosis before menarche. The median age at menarche was 13 years, compared to 12.8 years in the German general population. A significant delay of menarche was seen in patients with pituitary radiation doses of ≧30 Gy (mean 13.6 years, SD 2.2) compared to <30 Gy (mean 12.5 years, SD 1.4, p = 0.05). Patients with additional spinal radiation were even older at menarche (mean 14.4 years, SD 2.5). Pelvic and pelvic-near radiation significantly delayed onset of menarche (mean 14.0 years, SD 1.9 and mean 14.3, SD 2.6, respectively, p < 0.001). Only some chemotherapeutic agents (carboplatin/cisplatin, etoposide) were associated with a menarcheal delay of <1 year. Conclusion: Overall, female childhood cancer survivors showed a normal menarcheal age. Pituitary radiation dosage of ≧30 Gy, spinal and pelvic radiotherapy were associated with a moderate delay in the occurrence of menarche.

Does pituitary radiotherapy increase the risk of stroke and, if so, what preventative actions should be taken?

Radiotherapy for pituitary adenomas is a well-established and effective treatment, but it has been linked to a number of complications, including an increased risk of cerebrovascular disease and mortality. Possible underlying mechanisms include the direct effects of radiation on cerebral vasculature and deficiencies in specific pituitary hormones. Higher administered dose of radiotherapy is one of the main predictors of stroke. Although treatment strategies for stroke prevention in patients treated with pituitary radiotherapy have not been studied, using the lowest effective radiation dose and ensuring hormone deficiencies are adequately treated may be beneficial in reducing the risk of stroke.