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"Endo-depression" in surgical patients: why surgeons may more effectively treat depression.

INTRODUCTION

Depression is more common for hospitalised patients. Given the fact that depression is rapidly increasing in numbers, it would be interesting if we could have measured how this mood disorder is progressing through years among hospitalised patients. Of course, all Hospitals are different. However, the causes of depression for a hospitalised patient may not be caused only by the old furniture of the ward they have to stay in, but other organic causes--and treatable ones may co-exist or prevail.

Surgical patients may feel depressed during their stay in Hospital or may have mood disorders months or years before the diagnosis of the surgical problem. A surgical operation may determine the route of depressive disorders, when they are caused by endocrine tumours or paraneoplastic syndromes.

In cases that depression is initiated after an operation or trauma, surgeons can help indirectly by helping to improve the patients' quality of life during the rehabilitation period. Also, the successful re-operation in colectomized patients with a temporary colostomy is more effective for depression than any drug. Alternatively, by avoiding an amputation in a patient with a critical problem of ischemia, the surgeon helps much more than the best psychiatrist. However, to advise the surgical patient for his mood disorder and get the help of a psychiatrist in time, is also a very important contribution that surgeons might undertake. For example, patients with extended burns that alter their prior icon, are obvious problems that may lead to depressive disorders in the future. On the other hand, trauma victims who were drivers/passengers in vehicles that were totally damaged, have the need for follow up by a specialist in psychology/psychiatry. Sometimes the economy of time, as done by the surgeon who informs patients and their families for their non surgical problems and possible complications, saves the patients from time, costs and suffering.

In patients with depression who are admitted in Surgical Departments, things are not easy. Because, if they already receive medication for depression, most surgeons categorise them in the chronic depressed without a second thought. Especially if other symptoms prevail, mood is not a problem that surgeon will deal with. In asymptomatic patients with depression only and neuroendocrine tumours, diagnosis may be succeeded very late. Also, if the family members do not inform properly the doctor who receives the history, the patient may leave from the surgical department without diagnosis and treatment. Alternatively, if this patient did have psychiatric problems in the past, then surgeons cannot really help. Accidentally contacted CT's and MRI examinations are the key of the therapy for many patients with obscure symptomatology; this way medical marketing helps this category of patients in a magic way.

Losing time in patients with tumours seems to be a very serious medical mistake. In high-volume Hospitals, when a surgical consultation is asked for a patient in a Psychiatric ward, at a very full day, then the only lucky thing for the patient is to be examined by the surgeon who always says: "Do an abdomen CT and then call me back". This consultation may not be the one expecting from the good doctor, but this kind of surgeon will only help! Dyspepsia, losing some kilos and feel somehow depressed, may mean nothing and may be the only finding of a serious problem. Hypochondriasis is thought to be a very common diagnosis made by a short examination in women at the age of pre-menopause or older by very busy surgeons who simply don't find anything by the abdomen examination.

In Greece, many patients who lose weight and don't have the same appetite as always go to Surgical Outpatient Clinics asking for a complete diagnostic control, with the fear of having cancer. The behaviour of surgeons varies from clinical examination only to a super-complete examination with a full radiologic examination that eventually helps the patient. For people who left the Hospital with a clinical examination only, and after some months a diagnosis of cancer was revealed, many problems may occur with the families and doctors of the Outpatient Clinics. Especially Greek patients are accustomed to visit 2-3 medical doctors so that they will be sure that their cancer-phobia was not based on a real cancer. Many patients connect thyroid with their mood disorders, and they first investigate this option on their own diagnostic plan, in private laboratories.

Neuroendocrine tumours and Depression

Atypical depression is one of the manifestations of Cushing's Syndrome. In atypical depression we find hyperphagia, nervousness, hypersomnia and fatigue that are related with the low secretion of CRH (Corticotrophin Releasing Hormone). (1) If a patient with atypical depression has low levels of CRH this indicates that the cause is a Cushing's Syndrome, seasonal depressive disorders, fibromyalgia, post delivery depression, and other rare causes. (2)

Because Cushing's syndrome is characterized by increased morbidity and mortality, it is important to have an early diagnosis. The hypercortisolaemia may become chronic in mild Cushing's syndrome and this may cause a reduction in the hippocampus volume, which is caused by the hyperactivity of the HPA (Hypothalamus -Pituitary- Adrenals) Axis. This finding is present in other HPA hyperactivity syndromes, including major depression. However, there is not a close relationship of hippocampus volume and depression in general' The frequency of psychiatric disorders in patients with Cushing's syndrome is approximately 62% and there are patients who are diagnosed many years after the onset of the disease. Also, the differential diagnosis of hypercortisolaemia with vague symptoms is a common problem of endocrinologists.

A new period starts for the patient with Cushing's syndrome after a surgical operation. A period that needs all the team of medical doctors close to the patient, the endocrinologist, the surgeon, and the psychiatrist, and for patients who live in rural areas, the family doctor. The reverse of the symptoms is succeeded gradually and in a degree that varies according to the cortisol secretion postoperatively and other secondary factors. It has been found that in the 3 first months after the operation for Cushing's syndrome, the total psychopathology remains in a percentage of 53% of patients, in 6 months symptoms are decreasing to 36% and in the end of the first year to 24,1%. The recovery of HPA axis is confirmed with the use of stimulation tests with the use of ACTH (Adrenocorticotropic Hormone). It has been observed that the psychological improvement is related adversely with the basic morning cortisol secretion, but there is not correlation of the cortisol level that is produced with ACTH stimulation in 60 minutes. In the postoperative period in patients with Cushing's syndrome, depressive disorder is the predominant disorder among the observed psychiatric problems. Important to be highlighted is the fact that suicide idealism and panic crises are increased in the number postoperatively. The fact that depression exists in both pre- and postoperative periods, while cortisol has been corrected, may be caused by the inhibition of CRH production by the chronic cortisol appearance in the blood circulation. The mild increase of panic disorder after the correction of cortisol is related to the reduced chemical connection of glucocorticoids in the central sympathetic system. With time, an improvement in depressive symptoms are occurring, but the panic crises as well as the suicide idealism is to be taken seriously during the postoperative follow up. (2)

In children with Cushing's syndrome, there is brain atrophia, with memory disorders and depression. After the brain adenoma excision, rehabilitation may be total or partial. It has been found with MRI imaging that adenoma increasing for 5 years (meantime) in children, then the brain volume is lower, and there is enlargement of the celiac system and atrophia of the amygdaloid nuclei. There is not a difference in IQ or psychopathology in comparison to healthy children. One year after the adenoma excision the reverse of MRI findings is succeeded. However, a considerable IQ lowering is produced (Wechsler IQ score) and lower performance at school in comparison to other healthy children. The glucocorticoid effects in the brain of children seem to be different than in adulthood. (4)

Depressive symptoms are present in patients with glucagonoma. Glucagonoma is an alpha-islet cell tumour of the pancreas. These tumours are very rare and the only way to think about it in a patient with depressive disorder is if we find a mild increase in blood glucose (found >90% of cases) and the characteristic necrolytic migratory erythema, which are met in the 70% of cases. In case we find these 3 findings in a patient (depression, mild glucaemia, necrotic skin lesions), then we should ask for a glucagon level examination. In small Hospitals, that cannot contact this examination, the biopsy of skin lesions will be very useful. (5)

In patients with a carcinoid tumour, depression has been correlated with the treatment with INF-a, and are well helped with anti-depressive drugs. (6)

Cancer, paraneoplastic syndromes and depression

In patients with cancer, the mean prevalence of depression is 25% but it has been found that depression can be found in the high percentage of 40-50% of patients with pancreatic cancer or pharyngeal cancer. (7) In undiagnosed patients, cancer cachexia may be thought to be caused by depression. According to research studies in pancreatic cancer depression is more common even if compared to patients with advanced gastric cancer. The start of treatment after the depression diagnosis with antidepressive drugs and psychotherapy has been found to improve quality of life, pain and total survival. (7)

In pancreatic cancer, it has been found that atypical symptoms including depressive symptoms, anorexia and smoking or alcohol aversion, are observed 8-20 months before the clinical appearance of the disease with pain and /or jaundice, in 50% of cases. (8) The international study held by ESPAC (European Study Group of Pancreatic Cancer) (9) shows that early diagnosis has a strong impact on final survival. (10)

Depression in a patient with metastatic cancer is thought to be related with the endocrine status of a patient at the onset of treatment, according to studies done at advanced kidney cancer and metastatic melanoma. (11) The communication level of the patient with the doctors shows that it may help to face the danger of developing depression. (12)

Paraneoplastic syndromes come from tumours that produce and secrete hormone like substances. The amounts of these substances are many times uncontrollable resulting in homeostatic imbalance and the manifestation of clinical symptoms. The most common paraneoplastic disorder is hypercalcaemia which is 10-20% of cancer cases. Depression as paraneoplastic disorder is not easy to be recognized.

Especially today, that depressive disorders are very common, paraneoplastic depressive symptoms won't be diagnosed. If the patient is examined in a Hospital, only then pathologic finding may help.

The Ectopic Cushing's Syndrome may cause depressive symptoms as part of a paraneoplastic syndrome. In case there is an ectopic secretion of ACTH we do not find the clinical appearance of Cushing's Syndrome (moon face, buffalo neck, thinning of the skin, purple stretch marks,) so depressive disorder will be the only finding and hypercortisolaemia will not be found easily (because doctors will not examine it). The micro-cell cancer of lungs is responsible for the 50% of this syndrome. The metyrapone test and the stimulation test with CRH are contacted for the differential diagnosis from pituitary or adrenal tumours. The chromogranin A level comprises a marker that indicates the ectopic production of ACTH. (13)

Anorexia caused by surgical diseases and depression

Tumours that do not manifest with special symptoms at the disease onset may have as first symptom anorexia and mild weight loss for 6-8 months. This can be seen in gastric cancer, in small bowel cancer, and in pancreatic cancer. Especially when a tumour is situated at the pancreas neuropsychiatric disorders may appear. The tumours of the tail of the pancreas do not cause jaundice until they get large and may have an obscure development for long without any symptoms except atypical problems like weight loss and depressive symptoms. Also, chronic pancreatitis that is a risk factor for the development of pancreatic cancer presents with behavioral and mood disorders. (14)

Cancer in elderly and depression

Differential diagnosis problems may occur in patients with chronic pain who may also develop a malignancy. The ovarian cancer may be presented in old women as chronic pelvic pain. However, this kind of pain may be related with post-menopausal depression. The instructions for the pre-symptomatic control for cancer are vague after the age of 65 years old, according to classical manuals, and cases like ovarian cancer with depression and pelvic pain may be not diagnosed if it is treated as a psychiatric problem. The frequency pick of ovarian cancer is 70 years old and its prognosis is bad.

Hormone dependent cancer and depression

Breast cancer is the first to cancers that have been studied for their psychosocial dimensions. One out of 8 women suffers from breast cancer and depression is expected to happen because breast is related to sexuality and self-confidence. Post-mastectomy depression is frequently diagnosed early. Older studies refer that psychologic problems like depression and anxiety disorders were developed in 10-56% of operated women during the first 2-year post mastectomy. (15) In operated women after 2 years, the quality of life is better and equal with women who did not have a mastectomy. (16) The role of surgery became very important when minimal operations improved the aesthetic result after the suggestion of Umberto Veronesi and the National Anticancer Centre of WHO in Milan in 1968; this led to the broad acceptance of minimal operations (segmentectomy) for breast cancer surgery, and the oncologic results remained equally radical. (17) Thus, a new era began in the issue depression and breast cancer, with protagonist contributions of the surgeons and not of psychiatrists. One important improvement was the use of silicone for the aesthetic surgical rehabilitation in very short time after the operation, so operated women did not feel the loss of the breast in their somatic image. (18)

Depression related to tamoxifen has been reported in women who receive this anti-oestrogen for advanced breast cancer. This drug had negative effects in sexuality and self-confidence of women, probably due to weight increase and vaginal atrophia. (19)

Prostate cancer is a hormone dependent disease and its prognosis is directly related with the androgen levels in blood. About the 95% of androgens comes from the testes and the 5% is produced by adrenals. The GhRH -As (Gonadotropin hormone-releasing hormone analogs) cause the pharmaceutical orchectomy by prohibiting the androgen secretion from the testes. Nonsteroidal antiandrogens (NSAAs) cause inhibition of the androgens secreted by adrenals by blockade of their receptors. After radical prostatectomy, when it is possible, in advanced prostate cancer, we apply combined hormonal treatment. Common complications of radical prostatectomy are urine incontinence and sexual dysfunction. The atrophy of pinus and sexual impotence as well as urine incontinence cause serious problems to patients' quality of life and psychology, with a 10% depression postoperatively as it was found in men operated for prostate cancer 32 months--meantime--before the investigation. (20) The role of a surgeon in prostate cancer is very important as the prostatectomy with nerve preservation leads to improved quality of life in the operated patients. Robotic surgery seems to help in the improvement of this technique. (21) Also, a new technique, the male sling, treats the patient from the urine incontinence and improves his quality of life. (22)

Benign causes of depression in the surgical patient

Hypothyroidism is accompanied by depressive symptoms and memory problems. Also, in hyperthyroidism, we may see similar clinical findings, especially in elderly. The recovery of thyroid function results to the recovery from depressive symptoms but sometimes antidepressive medication is needed. Cases of subclinical hypothyroidism with depressive symptoms are common and are corrected with thyroxine only. Studies show that subclinical types of thyroid diseases are not causes of depressive symptoms. (23)

In patients with chronic pancreatitis, there is intense pain with alterations in behavior and depressive mood. Although the patient is suffering from the abdominal pain, the clinical examination does not have findings. Because these patients are commonly alcoholics (>87%) the behavioral disorders may be thought to derive from alcoholism (if chronic pancreatitis is undiagnosed). The operation is contra-indicated in patients who have a serious depression with suicidal behavior and patients who continue to receive alcohol. Because pancreatic cancer is one of the long-term complications in chronic pancreatitis, and because weight loss is common in both, the question of differential diagnosis is constant and the anxiety is great for both the patient and the surgeon.

Secondary hypo-pituitarism may derive after brain damage (operation, trauma, infection). The development of brain damage has great relation with the prevention strategies applied by the surgeon who follows up with the patient. Among all other dimensions of rehabilitation after trauma or neurosurgery/neurologic infection, the hormonal complications are the ones that may not be diagnosed and may cause problems in the long term when the patient has returned to his home.

REFERENCES

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(2.) Dorn LD, Burgess ES, Friedman TC, Dubbert B, Gold PW, Chrousos GP. The longitudinal course of psychopathology in Cushing's syndrome after correction of hypercortisolism. J Clin Endocrinol Metabol1997;82:912-9.

(3.) Starkman MN, Gebarski SS, Berent S, Schteingart DE. Hippocampal formation volume, memory dysfunction and cortisol levels in patients with Cushing's syndrome. Biol Psychiatry 1992: 32: 756-65.

(4.) Merke DP, Giedd IN, Keil MF, Mehlinger SL, Wiggs EA. Holzer S, et al. Children experience cognitive decline despite reversal of brain atrophy one year after resolution of Cushing syndrome. J Clin Endocrinol Metab 2005;90:2531-6.

(5.) van Beek AP, de Haas ER, van Vloten WA, Lips CJ, Roijers JF, Canninga-van Dijk MR. The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. Ear J Endocrinol. 2004;151(5):531-7.

(6.) Larsson G, Sjdd6n PO, Oberg K, Eriksson B, von Essen L. Health -related quality of life, anxiety and depression in patients with midgut carcinoid tumours. Acta Oncol 2001;40(7):825831.

(7.) van den Beuken-van Everdingen MH, de Rijke JM, Kessels AG, Schouten HC, van Kleef M, Patijn J. Quality of life and non-pain symptoms in patients with cancer. J Pain Symptom Manage. 2009;38(2):216-33.

(8.) Gallo L, Tomasetti P, Mighoro M, Casadei R, Marrano D. Do early symptoms of pancreatic exist that can allow an earlier diagnosis? Pancreas 2001; 22: 210-3.

(9.) Bassi C, Stocken DD, Olah A, Friess H, Buckels J, Hickey H, Dervenis C,et al; European Study Group for Pancreatic Cancer (ESPAC). Influence of surgical resection and postoperative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial. Dig 2005; 22(5):353-63.

(10.) Christodoulou It. [Mortality and morbidity as countable values]. 2nd Hellenic Congress for Healthcare Management, Economics and Policies, 2006 [Abstract in GreeK].

(11.) Cohen L, de Moor C, Devine D, Baum A, Amato RJ. Endocrine Levels at the start of treatment are associated with subsequent psychological adjustment in cancer patients with metastatic disease. Psychosom Med 2001; 63:951-8.

(12.) Schofield P.E. Psychological responses of patients receiving a diagnosis of cancer. Annals of Oncology 2003; 14:48-53.

(13.) Ferrari L, Seregni E, Bajetta E, Martinetti A, Bombardieri E.The biological characteristics of chromogranin A and its role as a circulating marker in neuroendocrine tumours. Anticancer Res. 1999; 19(4C):3415-27.

(14.) Christodoulou It. From the prison to the operating theatre; A bloody solution for a homeless drug user. Psychiatry Journal; Supplement;2006 [Abstract in Greek].

(15.) Morris T, Greer HS, White P. Psychological and social adjustment to mastectomy: a two-year follow-up study. Cancer 1977; 77:2381.

(16.) Hughson AV, Cooper AF, McArdle CS, Smith DC. Psychosocial consequences of mastectomy: Levels of morbidity and associated factors. J Psychosom Med 1988; 32:383.

(17.) Fisher B, Bauer M, Margolese R, Poisson R, Pilch Y, Redmond C, et al. Five year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation for the treatment of breast cancer. N Engl J Med 1985;312:665.

(18.) Noone RB, Frazier TG, Hayward CZ, Skiles MS. Patient acceptance of immediate reconstruction following mastectomy. Plast Reconstruct Surg 1982:69:632-40.

(19.) Speer JJ, Hillenberg B, Sugrae DP, Blacker C, Kresge CL, Decker VB, Zakalik D, Decker DA. Study of sexual functioning determinants in breast cancer survivors. Breast J. 2005;11(6):440-7.

(20.) Kraft KH. Prevalence of Depression in Patients Following Radical Prostatectomy. Abstract book of American Urological Association (AUA) Annual Meeting 2005. Abstract 199.

(21.) Nilsson AE, Carlsson S, Laven BA, Wiklund NP. Karolinska prostatectomy: a robot-assisted laparoscopic radical prostatectomy technique. Scand J Urol Nephrol. 2006;40(6):453-8.

(22.) Twiss CO, Fischer MC, Nitti V W. Comparison between reduction in 24-hour pad weight, International Consultation on Incontinence-Short Form (ICIQ-SF) score, International Prostate Symptom Score (IPSS), and Post-Operative Patient Global Impression of Improvement (PGI-I) score in patient evaluation after male perineal sling. Neurourol Urodyn. 2007;26(1):8-13.

(23.) Roberts LM, Pattison H, Roalfe A. Is subclinical thyroid dysfunction in the elderly associated with depression or cognitive dysfunction? Ann Intern Med 2006; 145:573-81.

Irene Christodoulou

Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece & Medical School, Democritus University of Thrace, Alexandroupolis, Greece

Corresponding author: Irene Christodoulou, MD, We 8 Heronias Str, Sikies, 56626, Thessaloniki, Greece Tel. 000302310613736 e-mail: irene-christodoulou@hotmail.com
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Author:Christodoulou, Irene
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Date:Jul 1, 2009
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