GH replacement therapy associated with development of diabetes

Posted on EndocrineToday.com

Luger A. Diabetes Care. 2012;35:57-62.

 

The incidence of diabetes was increased in patients with growth hormone deficiency who were on growth hormone replacement therapy, according to researchers in Europe.

The researchers selected patients from KIMS — Pfizer International Metabolic Database. Patients were selected if they had severe adult-onset GH deficiency that was confirmed with a GH stimulatory test and naive to GH treatment. Patients with a history of Cushing’s disease or acromegaly or with diabetes at baseline were excluded.

 

The study included data from 5,143 patients. Plasma glucose, HbA1c values, lipid and insulin-like growth factor I concentrations and serum IGF-I measurements were obtained.

Five hundred twenty-three patients developed diabetes after a median of 1.7 years. Patients who developed diabetes were older, had higher BMI, waist circumference, waist-to-hip ratio and triglyceride concentrations. They also had higher systolic and diastolic blood pressure and lower HDL cholesterol.

The incidence of diabetes was 2.6/100 patient-years, decreasing from 4.1/100 patient-years during the first year of GH replacement therapy to 1/100 patient-years after more than 8 years of treatment. The overall observed cases/expected cases ratio was 6, decreasing from 10.8 in the first year of treatment to 1.9 after 8 or more years of treatment.

Sex, BMI, attained age during follow-up, years between pituitary diagnosis and GH treatment start and years since first treatment were significantly associated with diabetes occurrence. There was no significant association with GH dose. In patients who did not develop diabetes, plasma glucose concentrations increased from 84.4 mg/dL to 89.5 mg/dL, and HbA1c levels increased from 4.74% to 5.09% after 6 years of treatment.

“Despite widely demonstrated benefits of growth hormone replacement treatment in adult growth hormone deficiency, a marked increase in the risk of developing diabetes must be considered,” the researchers wrote. “All patients, but particularly those with an adverse risk profile, should be carefully followed regarding parameters of glucose metabolism.”

From http://www.endocrinetoday.com/view.aspx?rid=91303

 

 

Patients Diagnosed With Severe Adult GH Deficiency Using The Insulin Tolerance Test, Arginine Or Glucagon Stimulation Tests Share Similar Clinical Features

PDF (277.1 KB)

Authors

Andy Toogood, MD, FRCP¹, Georg Brabant, MD, PhD FRCP², Dominique Maiter, MD, PhD³, Björn Jonsson, PhD⁴, Ulla Feldt-Rasmussen, MD, PhD⁵, Maria Koltowska-Haggstrom, PhD⁶, Ase Krogh Rasmussen, MD, PhD⁵, Michael Buchfelder, MD⁷, Bernhard Saller, MD, PhD⁸, Beverly M K Biller, MD⁹

¹Department of Endocrinology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, B15 2TH, United Kingdom
² Experimental and Clinical Endocrinology, MedizinischeKlinik I, RatzeburgerAllee 160, D-23538, Lübeck, Germany
³Department. of Endocrinology, CliniquesUniversitaires Saint-Luc, Avenue Hippocrate, 54.74, 1200 Brussels
⁴Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden
⁵Department of Medical Endocrinology, Rigshospitalet, Copenhagen, 2100, Denmark
⁶KIMS Pfizer Endocrine Care, Specialty Business Unit, Pfizer Health AB, Sollentuna, 190 91, Sweden
⁷Department of Neurosurgery, University of Erlangen Nuernberg, Erlangen, 91045, Germany
⁸ Pfizer Endocrine Care Europe, Tadworth, United Kingdom
⁹Neuroendocrine Unit, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, Boston, MA 02114, United States

Abstract

 

Objective: To determine whether the ITT, arginine (AST) and glucagon stimulation tests (GST) identify patients who have similar features of GH deficiency using a diagnostic threshold of 3 μg/l.

Patients and Methods: 5453 tests were available from 4,867 patients registered in the KIMS database (49.9% females, ITT = 3111, AST = 1390, GST = 952). Comparisons were made for GH peak, BMI, lipids, waist circumference, waist:hip ratio and quality of life (QoL-AGHDA questionnaire).

Results. There were significant (p<0.0001) intra-individual correlations between the GH peaks for the ITT vs AST (r = 0.655), ITT vs GST (r = 0.445) and AST vs GST (r = 0.632). GH peaks in response to all tests were negatively correlated to the number of additional pituitary hormone deficiencies, and positively correlated to IGF-I SDS. BMI had a negative influence on all three tests.

Comparing GHD patients according to the diagnostic test used, most clinical variables did not differ between the groups. The only exceptions showing any difference were BMI being slightly higher in the AST and GST groups, triglyceride levels increased in the GST group, and IGF-I SDS was lower in the ITT and AST than in the GST group. Waist circumference was larger and quality of life was worse in the GST group than in the other groups.

Conclusions. This study demonstrates that the ITT, AST and GST produce similar GH peaks, are influenced by similar clinical factors and identify patients with similar features of GH deficiency at a diagnostic threshold of 3 μg/L.

 

Keywords

Growth hormone deficiency, ITT, stimulation tests, glucagon, arginine, clonidine, IGF-I

Show References

 

From http://aace.metapress.com/content/h4228513un4m6370/

Growth Hormone improves stroke recovery

A hormone naturally produced by the body has been found to greatly improve long-term recovery rates following a stroke, writes Siski Green

Researchers at the Sahlgrenska Academy in Gothenburg assessed the progress of 407 patients aged between 18 and 70; all had all had a stroke and were then followed for two years afterwards. Measuring levels of a specific hormone – insulin-like growth factor 1 (IGF-1) -  the researchers found that patients who recovered most successfully also had higher levels of the hormone. This remained true for up to two years after the stroke.

The IGF-1 hormone is naturally higher in people who exercise often but levels are also affected by other growth hormones, heredity and nutrition, say the researchers. Body mass index also affects a person’s IGF-1 levels. It’s a hormone that plays in an important role in growth during childhood and it naturally declines with age, but although it appears linked to longevity (some animal studies have indicated it has a positive effect), no studies have been able to show whether it has a negative or positive impact on longevity in humans.

The researchers say that their results may help explain why patients who do more regular exercise, including physiotherapy, are more likely to make better progress than those who don’t. Now they plan to assess whether drug treatments that artificially raise the levels of IGF-1 could also help with recovery after a stroke.

From http://www.saga.co.uk/health/news/hormone-improves-stroke-recovery-254.asp

Adult Growth Hormone Deficiency: Unreplaced Sex Steroid Deficiency, Corticotropin Deficiency, and Lower IGF-I Are Associated with Lower Bone Mineral Density in Adults with Growth Hormone Deficiency

Nicholas A. Tritos, Susan L. Greenspan, Donna King, Amir Hamrahian, David M. Cook, Peter J. Jönsson, Michael P. Wajnrajch, Maria Koltowska-Häggstrom and Beverly M. K. Biller

Neuroendocrine Unit (N.A.T., B.M.K.B.), Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114; Department of Medicine (S.L.G.), University of Pittsburgh, Pittsburgh, Pennsylvania 15260; Department of Endocrinology, Diabetes, and Metabolism (A.H.), Cleveland Clinic, Cleveland, Ohio 44195; Department of Endocrinology (D.M.C.), Oregon Health & Science University, Portland, Oregon 97239; KIMS Medical Outcomes (P.J.J., M.K.-H.), Pfizer Endocrine Care, 191 90 Sollentuna, Sweden; and Pfizer Inc. (D.K., M.P.W.), New York City, New York 10017

Address all correspondence and requests for reprints to: Nicholas A. Tritos, M.D., D.Sc., Neuroendocrine Unit, Massachusetts General Hospital, Zero Emerson Place, Suite 112, Boston, Massachusetts 02114. E-mail: ntritos@partners.org.

Context: GH deficiency (GHD) is associated with low bone mineral density (BMD). Risk factors for lower BMD in this GHD population have not been fully elucidated. In particular, there are limited published data in GH-naïve subjects.

Objective: The objective of the study was to identify endocrine correlates of low BMD in treatment-naïve adult GHD subjects.

Design: This was a retrospective analysis of data extracted from the (Pfizer International Metabolic Study) KIMS database.

Setting: The study was an international epidemiological survey of more than 15,000 adult GHD patients from 31 countries.

Patients: A total of 1218 subjects with stringently defined GHD of adult onset (641 women and 577 men) who were GH naïve and had BMD measured in the posterior anterior lumbar spine and femoral neck by dual-energy X-ray absorptiometry.

Main Outcome Measures: Variables associated with standardized BMD (sBMD) in adult-onset GHD were examined.

Results: In the LS, body mass index (r = 0.13, P < 0.01), unreplaced sex steroid deficiency (r = –0.17, P < 0.0001), and corticotropin deficiency (r = –0.11, P < 0.01) were independently associated with sBMD. In the FN, age (r = –0.19, P < 0.0001), female gender (r = –0.18, P < 0.0001), body mass index (r = 0.21, P < 0.0001), and decreased IGF-I SD scores (r = 0.10, P < 0.001) were independently associated with sBMD.

Conclusions: Hormone variables associated with lower sBMD in patients with adult-onset GHD include unreplaced sex steroid deficiency and corticotropin deficiency in the LS and lower IGF-I SDS in the FN.

From http://jcem.endojournals.org/cgi/content/abstract/jc.2010-2662v1

Pegylated Long-Acting Human Growth Hormone Possesses a Promising Once-Weekly Treatment Profile, and Multiple Dosing Is Well Tolerated in Adult Patient

Esben Søndergaard, Marianne Klose, Mette Hansen, Birgit Sehested Hansen, Marianne Andersen, Ulla Feldt-Rasmussen, Torben Laursen, Michael Højby Rasmussen*, and Jens Sandahl Christiansen

Aarhus University Hospital (E.S., T.L., J.S.C.), DK-8000, Aarhus C, Denmark; Rigshospitalet (M.K., U.F.-R.), Copenhagen University, DK-2100, Copenhagen, Denmark; Odense University Hospital (M.H., M.A.), DK-5000, Odense, Denmark; and Global Development (B.S.H., M.H.R.), Novo Nordisk A/S, DK-2880 Bagsvaerd, Denmark

* To whom correspondence should be addressed. E-mail: mhr@novonordisk.com.

Background: Recombinant human GH (rhGH) replacement therapy in children and adults currently requires daily sc injections for several years or lifelong, which may be both inconvenient and distressing for patients. NNC126-0083 is a pegylated rhGH developed for once-weekly administration.

Objectives: Our objective was to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of NNC126-0083 in adult patients with GH deficiency (GHD).

Subjects and Methods: Thirty-three adult patients with GHD, age 20–65 yr, body mass index 18.5–35.0 kg/m2, and glycated hemoglobin of 8.0% or below. Fourteen days before randomization, subjects discontinued daily rhGH. NNC126-0083 (0.01, 0.02, 0.04, and 0.08 mg/kg) was given sc once weekly for 3 wk (NNC126-0083 for six subjects and placebo for two subjects). Blood samples were collected up to 168 h after the first and up to 240 h after the third dosing. Physical examination, antibodies, and local tolerability were assessed.

Results: NNC126-0083 was well tolerated with no difference in local tolerability compared with placebo and with no signs of lipoatrophy. A more than dose-proportional exposure was observed at the highest NNC126-0083 dose (0.16 mg protein/kg). Steady-state pharmacokinetics seemed achieved after the second dosing. A clear dose-dependent pharmacodynamic response in circulating IGF-I levels was observed [from a predose mean (SD) IGF-I SD score of -3.2 (1.7) to peak plasma concentration of -0.5 (1.3), 1.6 (1.3), 2.1 (0.5), and 4.4 (0.9) in the four dose groups, respectively].

Conclusion: After multiple dosing of NNC126-0083, a sustained pharmacodynamic response was observed. NNC126-0083 has the potential to serve as an efficacious, safe, and well-tolerated once-weekly treatment of adult patients with GHD.


From http://jcem.endojournals.org/cgi/content/abstract/jc.2010-1931v1

Is it possible to avoid hypopituitarism after irradiation of pituitary adenomas by the Leksell gamma-knife?

Josef Marek, Jana Jezkova, Vaclav Hana, Michal Krsek, Lubomira Bandurova, Ladislav Pecen, Vilibald Vladyka and Roman Liscak

J Marek, 3 Dept. of Medicine, Charles University in Prague, Prague, 128 08, Czech Republic
J Jezkova, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha 2, 12802, Czech Republic
V Hana, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
M Krsek, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
L Bandurova, Third Dept. of Medicine, First Medical Faculty, Charles University, Praha, Czech Republic
L Pecen, Institute of Informatics of the Czech Academy of Science, Praha, Czech Republic
V Vladyka, Dept. of Stereotactic and Radiation Neurosurgery, Hospital na Homolce, Praha, Czech Republic
R Liscak, Dept. of Stereotactic and Radiation Neurosurgery, Hospital na Homolce, Praha, Czech Republic

Correspondence: Jana Jezkova, Email: fjjezek@cmail.cz

Objective: Radiation therapy is one of the treatment options for pituitary adenomas. The most common side effect associated with Leksell gamma knife (LGK) irradiation is the development of hypopituitarism. The aim of this study was to verify that hypopituitarism does not develop if the maximum mean dose to pituitary is kept under 15 Gy and to evaluate the influence of maximum distal infundibulum dose on the development of hypopituitarism.

Design and methods: We followed the incidence of hypopituitarism in 85 patients irradiated with LGK in 1993-2003. The patients were divided in two subgroups: the first subgroup followed prospectively (45 patients), irradiated with a mean dose to pituitary < 15 Gy; the second subgroup followed retrospectively 1993-2001 and prospectively 2001- 2009 (40 patients), irradiated with a mean dose to pituitary > 15 Gy. Serum TSH, free thyroxine, testosterone or 17?–estradiol, IGF 1, prolactin and cortisol levels were evaluated before and every six months after LGN irradiation.

Results: Hypopituitarism after LGK irradiation developed only in one out of 45 (2.2%) patients irradiated with a mean dose to pituitary < 15 Gy, in contrast to 72.5% patients irradiated with a mean dose to pituitary >15 Gy. The radiation dose to the distal infundibulum was found as an independent factor of hypopituitarism with calculated maximum safe dose 17 Gy.

Conclusion: Keeping the mean radiation dose to pituitary under 15 Gy and the dose to the distal infundibulum under 17 Gy prevents the development of hypopituitarism following LGK irradiation.

 

From http://www.eje.org/cgi/content/abstract/EJE-10-0733v1

Magnetic Resonance Imaging and Pituitary Function in Children with Panhypopituitarism

Free Abstract Article (Fulltext) Article (PDF 148 KB)

---

Original Paper

Magnetic Resonance Imaging and Pituitary Function in Children with Panhypopituitarism
Guimei Li, Peng Shao, Xiaojun Sun, Qian Wang, Lijuan Zhang
Provincial Hospital Affiliated to Shandong University, Shandong, PR China

Address of Corresponding Author

Horm Res Paediatr 2010;73:205-209 (DOI: 10.1159/000284363)

---

 Key Words

• Magnetic resonance imaging
• Insulin-like growth factor-1
• Multiple pituitary hormone
• Panhypopituitarism

---

 Abstract

Background: To explore the relationship between magnetic resonance imaging (MRI) findings and multiple pituitary-target hormones in patients with panhypopituitarism or multiple pituitary hormone deficiency (MPHD).

Methods: 125 patients with MPHD (102 boys, MPHD group) and 90 age-, sex- and Tanner stage-matched normal children (control group) were enrolled. 96 of the patients with MPHD underwent MRI scans of the hypothalamic-pituitary area. The patients were subdivided into five stages according to their MRI findings. The serum concentrations of GH, IGF-1, FT₄, TSH, ACTH, cortisol, FSH, LH, prolactin, testosterone and estradiol were measured in patients and in controls.

Results: MRI stage was significantly positively correlated with the number of pituitary hormone deficiencies (r = 0.9, p < 0.001). MRI stage was negatively correlated with peak GH, IGF-1, FT₄, cortisol and anterior pituitary height (r = –0.43, –0.47, –0.67, –0.54, and –0.49, respectively, p < 0.01). Diabetes insipidus patients could be stratified according to their MRI stage; diabetes insipidus was found mainly in patients with absence of the posterior pituitary bright spot or small ectopic posterior pituitary bright spot on MRI.

Conclusion: An abnormal MRI finding is evidence of MPHD and, correspondingly, there is a noteworthy correlation between MRI and pituitary function.

Copyright © 2010 S. Karger AG, Basel

From http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowAbstract&ArtikelNr=284363&Ausgabe=253980&ProduktNr=224036

Mortality in Patients with Pituitary Disease

Mark Sherlock, John Ayuk, Jeremy W. Tomlinson, Andrew A. Toogood, Aurora Aragon-Alonso, Michael C. Sheppard, Andrew S. Bates,  and Paul M. Stewart*

Centre for Endocrinology, Diabetes, and Metabolism (M.S., J.A., J.W.T., A.A.T., A.A.-A., M.C.S., P.M.S.), School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TH, United Kingdom; and Birmingham Heartlands and Solihull National Health Service Trust (A.S.B.), Birmingham B9 5SS, United Kingdom

* To whom correspondence should be addressed. E-mail: P.M.Stewart@bham.ac.uk.

Pituitary disease is associated with increased mortality predominantly due to vascular disease. Control of cortisol secretion and GH hypersecretion (and cardiovascular risk factor reduction) is key in the reduction of mortality in patients with Cushing's disease and acromegaly, retrospectively.

For patients with acromegaly, the role of IGF-I is less clear-cut. Confounding pituitary hormone deficiencies such as gonadotropins and particularly ACTH deficiency (with higher doses of hydrocortisone replacement) may have a detrimental effect on outcome in patients with pituitary disease. Pituitary radiotherapy is a further factor that has been associated with increased mortality (particularly cerebrovascular). Although standardized mortality ratios in pituitary disease are falling due to improved treatment, mortality for many conditions are still elevated above that of the general population, and therefore further measures are needed.

Craniopharyngioma patients have a particularly increased risk of mortality as a result of the tumor itself and treatment to control tumor growth; this is a key area for future research in order to optimize the outcome for these patients.

From http://edrv.endojournals.org/cgi/content/abstract/er.2009-0033v1

Long-Term Results of Stereotactic Radiosurgery in Secretory Pituitary Adenomas

Frederic Castinetti, Mariko Nagai, Isabelle Morange, Henry Dufour, Philippe Caron, Philippe Chanson, Christine Cortet-Rudelli, Jean-Marc Kuhn, Bernard Conte-Devolx, Jean Regis and Thierry Brue

Service d’Endocrinologie, Diabète, et Maladies Métaboliques, et Centre de Reference des Maladies Rares d’Origine Hypophysaires (F.C., I.M., B.C.-D., T.B.), Hôpital de la Timone, F-13385 Marseille, France; Service de Neurochirurgie Fonctionnelle Stereotaxique (M.N., J.R.), and Service de Neurochirurgie, Hôpital de la Timone, F-13385 Marseille, France; Service d’Endocrinologie (H.D.), Maladies Métaboliques, Nutrition (P.Ca.), Centre Hospitalier Universitaire (CHU) de Toulouse, Hôpital Larrey, Pôle Cardio-Vasculaire et Métabolique, F-31059 Toulouse Cedex 9 France; Assistance Publique-Hôpitaux de Paris (P.Ch.), Service d’Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, Université Paris Sud 11, Institut National de la Santé et de la Recherche Médicale (INSERM) Unité 693, F-94275 Le Kremlin-Bicêtre, France; CHU de Lille (C.C.-R.), F-59130 Lambersart, France; and Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (J.-M.K.) INSERM Unité 413, Unité Associée Centre National de la Recherche Scientifique, CHU de Rouen, F-76230 Bois-Guillaume, France

Address all correspondence and requests for reprints to: Prof. T. Brue, Department of Endocrinology, Hôpital de la Timone, 264 rue St Pierre, cedex 5, 13385 Marseille, France. E-mail: thierry.brue@mail.ap-hm.fr.

Context: To date, no study reported long-term follow-up results of gamma knife stereotactic radiosurgery (SR).

Objective: The aim of the study was to determine long-term efficacy and adverse effects of SR in secreting pituitary adenomas.

Design: We conducted a retrospective study of patients treated by SR in the center of Marseille, France, with a follow-up of at least 60 months.

Patients: A total of 76 patients were treated by SR for acromegaly (n = 43), Cushing’s disease (CD; n = 18), or prolactinoma (n = 15) as a primary (n = 27) or adjunctive postsurgical treatment (n = 49).

Main Outcome Measures: After withdrawal of antisecretory drugs, patients were considered in remission if they had mean GH levels below 2 ng/ml and normal IGF-I (acromegaly), normal 24-h urinary free cortisol, and cortisol less than 50 nmol/liter after low-dose dexamethasone test (CD) or two consecutive normal samplings of prolactin levels (prolactinoma).

Results: After a mean follow-up of 96 months, 44.7% of the patients were in remission. Mean time to remission was 42.6 months. Twelve patients presented late remission at least 48 months after SR. Two patients with CD presented late recurrence 72 and 96 months after SR. Forty percent of patients treated primarily with SR were in remission. Target volume and initial hormone levels were significant predictive factors of remission in univariate analysis. Radiation-induced hypopituitarism was observed in 23% patients; in half of them, hypopituitarism was observed after a mean time of 48 to 96 months. Twenty-four patients were followed for more than 120 months; rates of remission and hypopituitarism were similar to the whole cohort.

Conclusions: SR is an effective and safe primary or adjunctive treatment in selected patients with secreting pituitary adenomas.

 

From http://jcem.endojournals.org/cgi/content/abstract/94/9/3400

Growth hormone replacement in adults: interactions with other pituitary hormone deficiencies and replacement therapies

Helena Filipsson and Gudmundur Johannsson

H Filipsson, Endocrinology, Göteborg, Sweden
G Johannsson, Endocrinology, Medicin, Gothenburg, SE-413 45, Sweden

Correspondence: Gudmundur Johannsson, Email: gudmundur.johannsson@gu.se

Severe growth hormone deficiency (GHD) in adults has been described as a clinical entity. Some of the features associated with GHD could, however, be due to unphysiological and inadequate replacement of other pituitary hormone deficiencies. This may be true for glucocorticoid replacement that lacks a biomarker making dose titration and monitoring difficult.

Moreover, oral oestrogen replacement therapy decreases insulin growth factor 1 (IGF-I) levels compared to transdermal route, which attenuates the responsiveness to GH replacement therapy in women. In addition, in untreated female hypogonadism, oral oestrogen may augment the features associated with GHD in adult women. Important interactions between the hormones used for replacing pituitary hormone deficiency occur. Introducing GH replacement may unmask both an incipient adrenal insufficiency and central hypothyroidism.

Therefore, awareness and proper monitoring of these hormonal interactions are important in order to reach an optimal replacement therapy. This review will focus on the complex hormonal interactions between GH and other pituitary hormones in GHD and in GH replacement.

From http://www.eje.org/cgi/content/abstract/EJE-09-0319v1

Long-Term Results Of Stereotactic Radiosurgery In Secretory Pituitary Adenomas

Frederic Castinetti, Mariko Nagai, Isabelle Morange, Henry Dufour, Philippe Caron, Philippe Chanson, Christine Cortet-Rudelli, Jean-Marc Kuhn, Bernard Conte-Devolx, Jean Regis,  and Thierry Brue*

Service d'Endocrinologie, diabète et maladies métaboliques, et Centre de reference des maladies rares d'origine hypophysaires DEFHY, Hôpital de la Timone, Marseille, France; Service de neurochirurgie fonctionnelle stereotaxique, Hôpital de la Timone, Marseille, France; Service de Neurochirurgie, Hôpital de la Timone, Marseille, France; Service d'Endocrinologie - Maladies métaboliques – Nutrition - CHU de Toulouse - Hôpital Larrey - Pôle Cardio-Vasculaire et Métabolique - 24 Chemin de Pouvourville TSA 30030 FR-31059 TOULOUSE CEDEX 9 France; Assistance Publique-Hôpitaux de Paris, Service d'Endocrinologie et des Maladies de la Reproduction, Hôpital de Bicêtre, Université Paris Sud 11, INSERM U693. F-94275 Le Kremlin-Bicêtre, France; Centre Hospitalier Universitaire de Lille, 58 Avenue de l'Amiral Courbet FR-59130 LAMBERSART France; Institut Fédératif de Recherches Multidisciplinaires sur les Peptides - INSERM U 413 - UA CNRS IFRMP 23- CHU de Rouen - 147 Avenue du Maréchal Juin - FR-76230 BOIS-GUILLAUME France

* To whom correspondence should be addressed. E-mail: thierry.brue@mail.ap-hm.fr.

Context: To date, no study reported long-term follow-up results of Gamma Knife stereotactic radiosurgery (SR).

Objective: To determine long-term efficacy and adverse effects of SR in secreting pituitary adenomas.

Design: Retrospective study of patients treated by SR in the center of Marseille, France, with a follow-up at least equal to 60 months.

Patients: 76 patients were treated by SR for acromegaly (n=43), Cushing's disease (CD, n=18) or prolactinoma (n=15), as a primary (n=27) or adjunctive post-surgical treatment (n=49).

Main Outcome Measures: After withdrawal of antisecretory drugs, patients were considered in remission if they had mean GH levels < 2 ng/ml and normal IGF1 (acromegaly), normal 24h urinary free cortisol and cortisol < 50 nmol/l after low dose dexamethasone test (CD), or 2 consecutive normal samplings of prolactin levels (prolactinoma).

Results: After a mean follow-up of 96 months, 44.7% of the patients were in remission. Mean time to remission was 42.6 months. Twelve patients presented late remission at least 48 months after SR. Two patients with CD presented late recurrence 72 and 96 months after SR. Forty percent of patients treated primarily with SR were in remission. Target volume and initial hormone levels were significant predictive factors of remission in univariate analysis. Radiation-induced hypopituitarism was observed in 23% patients; in half of them, hypopituitarism was observed after a mean time of 48 to 96 months. Twenty-four patients were followed more than 120 months: rates of remission and hypopituitarism were similar to the whole cohort.

Conclusions: SR is an effective and safe primary or adjunctive treatment in selected patients with secreting pituitary adenomas.

Key words: gamma knife • radiosurgery • stereotactic radiosurgery • radiotherapy • acromegaly • Cushing's disease • prolactinoma

From http://jcem.endojournals.org/cgi/content/abstract/jc.2008-2772v1

Third Anniversary of My Kidney Cancer Surgery

From my bio at http://www.cushings-help.com/maryos_story.htm

(originally posted 3 years ago) ...My endo appointment is over. Turns out that the argenine test that was done 2 years ago was done incorrectly. The directions were written unclearly and the test run incorrectly, not just for me but for everyone who had this test done there for a couple years. My endo discovered this when he was writing up a research paper and went to the lab to check on something.

So, I'm off GH again for 2 weeks, then I'm supposed to be retested. The "good news" is that the argenine test is only 90 minutes now instead of 3 hours.

Update June 2, 2006

Wow, what a nightmare my argenine retest started! I went back for that Thursday, April 27, 2006. Although the test was shorter, I got back to my hotel and just slept and slept. I was so glad that I hadn't decided to go home after the test.

Friday I felt fine and drove back home, no problem. I picked up my husband for a biopsy and took him to an outpatient surgical center. While I was there waiting for the biopsy to be completed, I started noticing blood in my urine and major abdominal cramps. I left messages for several of my doctors on what I should do. I finally decided to see my PCP after I got my husband home.

When Tom was done with his testing, his doctor took one look at me and asked if I wanted an ambulance. I said no, that I thought I could make it to the emergency room ok - Tom couldn't drive because of the anaesthetic they had given him. I barely made it to the ER and left the car with Tom to park. Tom's doctor followed us to the ER and became my new doctor.

They took me in pretty fast since I was in so much pain, and had the blood in my urine. They thought it was a kidney stone. After a CT scan, my new doctor said that, yes, I had a kidney stone but it wasn't the worst of my problems, that I had kidney cancer. Wow, what a surprise that was! I was admitted to that hospital, had more CT scans, MRIs, bone scans, they looked everywhere.

My open radical nephrectomy was May 9, 2006 in another hospital from the one where the initial diagnosis was made. My surgeon felt that he needed a specialist from that hospital because he believed preop that my tumor had invaded into the vena cava because of its appearance on the various scans. Luckily, that was not the case.

My entire left kidney and the encapsulated cancer (10 pounds worth!) were removed, along with my left adrenal gland and some lymph nodes. Although the cancer (renal cell carcinoma AKA RCC) was very close to hemorrhaging, the surgeon believes he got it all. He said I was so lucky. If the surgery had been delayed any longer, the outcome would have been much different. I will be repeating the CT scans every 3 months, just to be sure that there is no cancer hiding anywhere. As it turns out, I can never say I'm cured, just NED (no evidence of disease). This thing can recur at any time, anywhere in my body.

I credit the argenine re-test with somehow aggravating my kidneys and revealing this cancer. Before the test, I had no clue that there was any problem. The argenine test showed that my IGF is still low but due to the kidney cancer I cannot take my growth hormone for another 5 years - so the test was useless anyway, except to hasten this newest diagnosis...

So, here we are 3 years later...

I find it amazing in a way.  The time seems to feel like more than 3 years.  Yet, had I been told I had 3 years to live back then, I would have seemed like a short time.  Amazing, the tricks that time can play.

I wish I could say that I feel wonderful now but I can't.  My energy levels are still so low and my temporary part-time job isn't helping.

Because the one adrenal gland I have isn't working and the other is gone, I'm still taking cortisol, although much less than my endo wants me to take.  If I take more, I start gaining weight again.

I'm feeling almost Cushie - when I'm home I'm sleeping but sometimes I's awake during the night, too.

I'm also eating more than normal, I think.  Not meals, but snacks, junky stuff.

Trisha Torrey wrote in her blog  about Patient Empowerment  a post titled An Ethical Conundrum - Should I Share This Information?  One of her questions was "How many patients, when given the choice between quality of life vs quantity of life, would choose quality anyway?"

Part of my response was "I want as much information as possible about my diseases and I want to be able to decide what do with that information...

I would much rather have a better quality of life than a longer one."

And it's true for me, today.  What is the point of hanging around for 20 or so more years if they're just spent sleeping?

True, I'm not in pain or anything but shouldn't there be more?  Am I just here to help other Cushing's patients?  I think I have enough started that future folks can help themselves.

I often see studies and clinical trials for Cushies and various drug  options.  And the cut-off date is always younger than I am.  Does this mean that possible future treatments wouldn't work for me?  Am I now too old to deserve a better quality of life?  What's the deal with that?

I know there are no answers to all this.  Maybe in my lifetime someone will come up with some answers to all this and I'll be out doing stuff.  I sure hope so!

But now it's time for a nap...

A Simple and Cost-Effective Approach to Assessment of Pituitary ACTH and GH Reserve – Combined Use of the Overnight Metyrapone Test and IGF-I Standard

http://jcem.endojournals.org/cgi/content/abstract/jc.2008-0154v1

A Simple and Cost-Effective Approach to Assessment of Pituitary ACTH and GH Reserve – Combined Use of the Overnight Metyrapone Test and IGF-I Standard Deviation Scores

Submitted on January 22, 2008
Accepted on July 22, 2008

A Simple and Cost-Effective Approach to Assessment of Pituitary ACTH and GH Reserve – Combined Use of the Overnight Metyrapone Test and IGF-I Standard Deviation Scores

James Gibney*, Marie-Louise Healy, Thomas P. Smith, and T. Joseph McKenna

Department of Endocrinology and Department of Medicine, St. Vincent's University Hospital Elm Park and The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland

* To whom correspondence should be addressed. E-mail: james.gibney@amnch.ie.

Context: The insulin tolerance test (ITT) is the gold standard for assessment of ACTH and growth hormone (GH) reserve in patients with suspected hypopituitarism. It is labour-intensive and costly.

Objective: To determine whether use of the overnight metyrapone test (OMT) and plasma IGF-I standard deviation scores (IGF-I-SDS) could provide a cost-effective alternative to the ITT.

Design: A retrospective chart review

Setting: A teaching hospital

Participants and intervention: Charts from 100 patients with organic pituitary disorders were reviewed. All underwent the OMT unless 9am plasma cortisol was <80>450 nmol/l when ACTH-deficiency or ACTH-sufficiency respectively was diagnosed. Patients were considered GH-deficient if the age-related IGF-I-SDS was <-3 or if they had 3 or more other pituitary hormone deficiencies (PHDs). Patients were considered GH-sufficient if age-related IGF-I-SDS was greater than the 95th centile established from patients with known GHD. Thirty-three underwent an ITT.

Main Outcome Measures: The proportion of patients in whom ACTH and GH reserve could be assessed using OMT/IGF-I-SDS. The concordance with results obtained from ITT.

Results: Fifty-five patients were ACTH-sufficient and 45 were ACTH-deficient. Twenty-one were GH-sufficient and 33 were GH- deficient based on IGF-I-SDS and other PHDs, while 46 could not be classified. There was near-uniform concordance between OMT/IGF-I-SDS and ITT. Initial investigation using OMT/IGF-I-SDS resulted in a significant cost saving. Conclusions: ACTH and GH reserve can be accurately and cost-effectively investigated using OMT/IGF-I-SDS in approximately 50% of patients with organic pituitary disorders.

Key words: Hypopituitarism • Overnight Metyrapone Test • IGF-I