a difficult to treat case of cushing s syndrome

Letters to the Editor Corresponding Author: Dr. Amitabh Sagar, Department of Internal Medicine, Armed Forces Medical College, Pune, Maharashtra, India E‑mail: amitthephysician@gmail.com References Feroze M, Arvindan KP, Jose L Gaucher’s disease among Mappila Muslims of Malabar Indian J Pathol Microbiol 1994;37:307‑11 Beutler E, Grabowski GA Glucosylceramide lipidosis–Gaucher disease In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors The Metabolic and Molecular Bases of Inherited Diseases 8th ed New York: McGraw‑Hill; 2001 p. 3635‑68 Ginsberg H, Grabowski GA, Gibson JC, Fagerstrom R, Goldblatt J, Gilbert HS, et al Reduced plasma concentrations of total, low density lipoprotein and high density lipoprotein cholesterol in patients with Gaucher type I disease Clin Genet 1984;26:109‑16 Bohra V, Nair V Gaucher’s disease Indian J Endocrinol Metab 2011;15:182‑6 Grabowski GA Phenotype, diagnosis and treatment of Gaucher disease Lancet 2008;372:1263‑71 Access this article online Quick Response Code: Website: www.ijem.in DOI: 10.4103/2230-8210.107881 A difficult to treat case of Cushing’s syndrome Sir, An 18‑year old girl presented in 1998 with clinical, biochemical, hormonal and radiological evaluation consistent with Cushing’s disease She underwent trans‑sphenoidal resection for pituitary microadenoma Serum cortisol level on third post‑operative day remained elevated She was re‑evaluated in June 2001 and underwent bilateral adrenalectomy in May 2002 She had marked improvement in her symptoms and was on steroid replacement In March 2003 her symptoms re‑appeared and glycemic control deteriorated She has already stopped steroid replacement Her basal cortisol done twice was elevated (32 and 38 µg/dl) with raised ACTH levels (98.7 pg/ml) MRI of pituitary showed a focal hypodense lesion and CT adrenal showed hyperplasia of right adrenal remnant [Figure 1] She underwent host of imaging studies to find missed ectopic ACTH secreting tumor, but were negative She was advised second trans‑sphenoidal surgery for which she refused She was started on tab ketoconazole, which she took intermittently Her cortisol levels done Figure 1: CT scan abdomen showing hyperplasia of right adrenal remnant every year, remained elevated Gamma knife instrument was installed in this hospital in 2007 In 2010, we persuaded her to undergo gamma‑knife surgery, which she refused However, on repeated persuasion she agreed, and underwent it in September 2011 After surgery her symptoms gradually improved In July 2012, she reported with persistent anorexia, vomiting, extreme asthenia with weight loss of about 20 kg Examination revealed hypotension and investigations showed hyponatremia Na‑129 meq/l, hyperkalemia K‑6.0 meq/l and hypoglycemia Her insulin requirement had come down by 50% with no need for anti‑hypertensive, and her cortisol was 2.6 µg/dl Finally she had developed adrenal insufficiency with possible permanent cure of Cushing’s disease This case highlights agony of patient and treating physician She had first failed pituitary surgery indicated by persistent hypercortisolemia She had recurrence even after bilateral adrenal surgery Recurrence after adrenalectomy may be due either to regrowth of adrenal cells in the surgical bed or growth of adrenal rest tissue Unsuccessful adrenalectomy is usually the consequence of failure to excise hyperplastic adrenal tissue extending around the right adrenal vein.[1] At this stage, a missed or occult ectopic‑ACTH secreting tumor was suspected Common causes of such slow growing tumor are thoracic carcinoid  (36‑49%), small cell carcinoma of lung (18‑37%) and others (15‑44%) like pancreatic carcinoid, pheochromocytoma and medullary thyroid carcinoma.[2] Her imaging studies for ectopic‑ACTH secreting tumor were negative Facilities for inferior petrosal sinus sampling were not available at this hospital at that time Options at his stage were second TSS, remnant adrenalectomy, radiotherapy or medical therapy Success rate of second TSS varies between 30 to 70% and predictors of success are correct diagnosis, initial incomplete TSS and residual tumor on CT/MRI However, in absence of biochemical evidence such focal defects in the pituitary gland on CT/ Indian Journal of Endocrinology and Metabolism / Jan-Feb 2013 / Vol 17 | Issue 181 Letters to the Editor MRI should not be taken as absolute evidence of presence of a corticotroph adenoma Radiation therapy takes prolong period for effect (1‑10 years), require medical therapy for intervening period and radiation induced hypopituitarism which will affect fertility Hence on refusal for surgery she was started on medical therapy Gamma knife therapy has been used in the treatment of Cushing’s disease as primary mode of therapy and after failed surgery.[3] During prolong course of illness with two failed surgery, it becomes difficult to persuade patient to undergo any intervention But we could persuade patient to undergo gamma‑knife surgery once it became available She responded with development of adrenal insufficiency after 9 months Several studies have been published in the use of gamma knife in functioning and non‑functioning pituitary microadenomas Remission rate defined by normalized 24hrs urinary cortisol levels ranged from 35 to 83% of cases.[3‑6] The efficacy of remission depended on the target volume[4] and the pre‑radiosurgery hormonal levels.[5] Lower target volume and low hormonal levels indicated higher the chances of remission The time to remission varied from 13 to 24 months Our patient went into adrenal insufficiency nine months post‑Gamma knife Hypopituitarism is the most frequent side effect frequently seen 12‑24 months post‑gamma knife decreasing after about 120 months.[6] She needs regular follow up for hypopituitarism So here we had a case that underwent TNTS, bilateral adrenalectomy, medical treatment and Gamma knife and finally achieved remission of disease 14 years after the diagnosis of Cushing’s disease suggesting there is light at the end of the tunnel M K Garg, Aditi Pandit, Sandeep Kharb Department of Endocrinology, Army Hospital (Research and Referral), Delhi Cantonment, India Corresponding Author: Dr. M K Garg, Department of Endocrinology, Army Hospital (Research and Referral), Delhi Cantonment ‑ 110 010, India E‑mail: mkgargs@gmail.com References 182 Young WF Jr, Thompson GB Laparoscopic adrenalectomy for patients who have Cushing’s syndrome Endocrinol Metab Clin North Am 2005;34:489‑99 Newell‑Price J Diagnosis/differential diagnosis of Cushing’s syndrome: A review of best practice Best Pract Res Clin Endocrinol Metab 2009;23:S5‑14 Kobayashi T, Kida Y, Mori Y Gamma knife radiosurgery in the treatment of Cushing disease: Long‑term results J Neurosurg 2002;97:422‑8 Jagannathan J, Sheehan JP, Pouratian N, Laws ER, Steiner L, Vance ML Gamma Knife surgery for Cushing’s disease J Neurosurg 2007;106:980‑7 Castinetti F, Nagai M, Morange I, Dufour H, Caron P, Chanson P, et al Long‑term results of stereotactic radiosurgery in secretory pituitary adenomas J Clin Endocrinol Metab 2009;94:3400‑7 Castinetti F, Régis J, Dufour H, Brue T Role of stereotactic radiosurgery in the management of pituitary adenomas Nat Rev Endocrinol 2010;6:214‑23 Access this article online Quick Response Code: Website: www.ijem.in DOI: 10.4103/2230-8210.107882 Endocrinopathy complicating a case of Tuberous sclerosis Sir, Tuberous sclerosis  (TSC) is a multi‑system genetic disorder affecting skin, brain/nervous system, kidneys, heart, and lung and leading to growth of non‑malignant tumors A combination of symptoms may include seizures, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the tumor suppressor proteins hamartin and tuberin, respectively A 26‑year‑old female with no premorbidities presented with complaints of galactorrhea for the past 10 days and menstrual irregularities over the past 6 months Galactorrhea was spontaneous Her last childbirth 4 years ago was uneventful She had no headache, vomiting, visual impairment She denied any history of substance abuse, drug intake (anti‑psychotic, anti‑emetic, hormonal preparations), hypothyroidism, chronic liver or kidney diseases, epilepsy There was no significant family history She was a well‑nourished female with mild pallor, tiny nodule on face, subungual fibroma in hands [Figures 1 and 2] There was spontaneous galactorrhea and mildly tender breasts without any signs of inflammation Systemic examination was entirely normal with normal IQ Ophthalmologic evaluation revealed white disk‑shaped retinal hamartoma Routine laboratory investigations including renal and liver function tests, thyroid profile were normal Serum prolactin was 85 ng/mL with FSH‑4.66 and LH‑4.21 mIU/ml In view of the theoretical possibility of involvement of cell groups of other anterior pituitary lineage, tests for evaluation of other anterior pituitary hormones were carried out and were found to be normal Abdominal and pelvic Indian Journal of Endocrinology and Metabolism / Jan-Feb 2013 / Vol 17 | Issue Copyright of Indian Journal of Endocrinology & Metabolism is the property of Medknow Publications & Media Pvt Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission However, users may print, download, or email articles for individual use  ... premorbidities presented with complaints of galactorrhea for the past 10 days and menstrual irregularities over the past 6 months Galactorrhea was spontaneous Her last childbirth 4 years ago was uneventful... finally achieved remission of disease 14 years after the diagnosis of Cushing? ? ?s disease suggesting there is light at the end of the tunnel M K Garg, Aditi Pandit, Sandeep Kharb Department of Endocrinology,... the treatment of Cushing disease: Long‑term results J Neurosurg 2002;97:422‑8 Jagannathan J, Sheehan JP, Pouratian N, Laws ER, Steiner L, Vance ML Gamma Knife surgery for Cushing? ? ?s disease J Neurosurg