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Psychological Aspects of Pituitary Tumors

By Nicoletta Sonino, Giovanni Favi, Franco Fallo, and Marco Boscaro. From The Institute of Semeiotica Medica, University of Padua, Italy and the Affective Disorders Program, Department of Psychology, University of Bologna, Italy.

The study of the interrelationships between the endocrine and psychic apparatus is displaying a curious tendency. On the one hand, the last decade has witnessed an upsurge of interest in the limbic-hypothalamic control of hormonal function. Such an area of research, often subsumed under the rubric of psychoneuroendocrinology, encompasses the use of pharmaceutical probes, the study of endocrine dysfunction in psychiatric illness (notably depression), laboratory research paradigms (e.g.) experimental stress, and the merging field of neuroimmunoendocrinology. On the other hand, the relationship of endocrine disease to psychological distress, despite an impressive body of research evidence [1-3], is largely neglected in the literature concerned with clinical endocrinology. Standard textbooks and journal reviews by and large ignore or only incidentally mention the psychiatric correlates of endocrine disorders. Clinical endocrinology seems to depart from other areas of medicine (e.g. cardiology) that have become increasingly concerned with the issues of psychological well-being, functional capacity and social and interpersonal aspects of medical illness, in the area of research defined as quality of life. [4].

As Lipowski [5] stated, `how a person experiences the pathological process, what it means to him, and how this meaning influences his behavior and interaction with others are all integral components of disease viewed as a total human response,'. We will try to outline some of the endocrine areas where an increased attention to the psychological aspects of disease may have important clinical and research implications.

Cushing [7] underscored the role of `psychic traumas' in pituitary disease, yet his leads were not followed by other investigators. In a recent study [8], stressful life events prior to illness onset were investigated by means of a semistructured research interview [9] in 30 healthy patients with Cushing's syndrome and 30 healthy controls. Losses, undesirable events, and uncontrolled events were significantly more frequent in patients than controls [8], similar to what had been found in major depression. When the objective negative impact and the likelihood of an event being the consequence of illness were evaluated by a blind rater, patients with Cushing's syndrome reported significantly more "negative" and "independent" events than controls. A pathogenetic role for recent life events in Cushing's disease in a final common pathway of genetic, neurophysiological, biochemical and behavioral events, was suggested. Life events might also be relevant in increasing individual vulnerability to relapse in Cushing's disease.

Unfortunately, despite several clinical observations, the contribution of recent life events to the onset of endocrine disorders such as hyperprolactinemia and polycystic ovary syndrome, has not been investigated in a controlled way by reliable probes. Schmale [10] remarks that the patient's history (trauma in childhood, poorly adapted family, anniversaries, etc.) is the most important step in evaluating the personal significance of the life setting. A biographic and clinical investigation of 101 patients with hyperprolactinemia and/or galactorrhea suggested that exposure during childhood to an environment characterized by an absent, alcoholic, or violent father may condition some women to develop and/or galactorrhea later in life as a response to specific environmental changes. Similarly, early neurotic traits, such as enuresis, were significantly more frequent in 20 women with hyperprolactinemic amenorrhea than in 21 patients with normoprolactinemic amenorrhea, suggesting a decreased catecholaminergic activity in reaction to stress....

Major depressive disorders are a severe and life-threatening complication of endocrine disorders such as Cushing's syndrome, Addison's disease, hyperthyroidism, hypothyroidism and hyperprolactinemic amenorrhea, as reviewed in detail elsewhere [2]. Other psychiatric symptoms, ranging from anxiety to psychotic disturbances and cognitive impairment may be present, even though to a lesser degree then depression. It is of interest that in other endocrine disorders, such as acromegaly [14] and hirsutism [15], an increased prevalence of psychiatric illness compared to general medical patients was not found. Starkman et al. [16] showed how the elevated levels of catecholamines secreted by pheochromocytomas are not sufficient to elicit an anxiety disorder. These data should point to the fact that the occurrence of an organic affective syndrome in endocrine disease may not simply be the consequence of increased hormonal levels, but the expression of a more general suprapituitary derangement. A depressed mood may have a profound influence on quality of life and on how a person experiences the endocrine disease process and his interactions with others. A treatment primarily directed to the physical condition may be more effective than antidepressant drugs in organic affective syndromes. Examples are provided by the effect of steroid synthesis inhibitors upon depression in Cushing's syndrome or by the action of antithyroid drugs on anxiety in hyperthyroidism [2]. On the other hand, clinical endocrinologists may tend to underestimate psychiatric symptoms as readily suppressible by adequate medical or surgical treatment....

Investigation on quality of life may herald a welcome psychosomatic approach in endocrine research and practice. The term "psychosomatic" refers to the postulate that the mind and body are two inseparably linked aspects which are differentiated for methodological and communicative purposes only [21] and that the person invariably functions, reacts and acts as an integrated mind-body unit [5]. Using Engel's [21] appraisal of current medical education, we may say that the average endocrinologist today completes his formal education with impressive capabilities to deal with most of the technical aspects of endocrine disease, yet when it comes to dealing with the psychosocial aspects of patient care "he displays little more than the native ability and personal qualities with which he entered medical school' [21, p. 169]. Further, the considerable body of knowledge about human behavior and affective disorders that has accumulated over the years lies as only marginal and incidental to hormonal disturbances, instead of fostering the biopsychosocial comprehension of endocrine disease. Cushing [7] wondered whether the "psychic instability or the disturbance on internal secretion" was the primary factor in pituitary disease. Time has come for a more wide-spread endorsement of his teachings.


  1. Reus VI: Behavioral disturbances associated with endocrine disorders. Ann Rev Med 1986;37:205-214.
  2. Fava GA, Sonino N, Morphy MA: Major depression associated with endocrine disease. Psychiat Dev 1987;4:321-348.
  3. Lobo A, Perez-Echeverria MJ, Jimenez-Azmarez A, Sancho MA: Emotional disturbanecs in endocrine patients. Br J Psychiatry 1988;152:807-812.
  4. Fava GA, Magnani B: Quality of life. A review of contemporary confusion. Med Sci Res 1988;16:1051-1054.
  5. Lipowski ZJ: Psychosocial aspects of disease. Ann Intern Med 1969;71:1197-1206.
  6. Miller TW (ed): Stressful Life Events. Madison, International Universities Press, 1989.
  7. Cushing H: Psychic disturbaences associated with disorders of the ductless glands. Am J Insanity 1913;69:965-990.
  8. Sonino N, Fava GA, Grandi S, Mantero F, Boscaro M: Stressful life events in the pathogenesis of Cushing's syndrome. Clin Endocrinol 1988; 29:617-623.
  9. Paykel ES: Methodology of life events research; in Fava GA, Wise TN (eds): Research Paradigms in Psychosomatic Medicine. Basel, Karger, 1987, pp. 13-29.
  10. Schmale AH: Importance of life setting for disease onset. Modern Treatment 1969;6:643-655.
  11. Nunes MCP, Sobrinho LG, Calhaz-Jorge C, Santos MA, Mauricio JC, Sausa MFF: Psychosomatic factors in patients with hyperprolactinemia and/or galactorrhea. Obstet Gynecol 1980;55:591-595.
  12. Fava M, Guaraldi GP, Borofsky GL, Mastrogiacomo I: Childhood's enuresis in the history of women with hyperprolactinemic, Int J Psychiat Med 1989;19:41-46
  13. Murphy E, Brown GW: Life events, psychiatric disturbance and physical illness. Br J Psychiatry 1980; 136:326-338.
  14. Abed RT, Clark J, Elbadawy MHF, Cliffe MJ: Psychiatric morbidity in acromegaly. Acta Psychiat Scand 1987;75:635-663.
  15. Fava, GA, Grandi S, Savron G, Bartolucci G, Santarsierno G, Trombini G, Orlandi C: Psychosomatic assessment of hirsute women. Psychother Psychosom 1989;51:96-100.
  16. Starkman MN, Zelnic TC, Nesse RM, Cameron OG: Anxiety in patients with pheochromocytomas. Arch Intern Med 1985;145:248-252.
  17. Marks I:Behaviral and drug treatments of phobic and obsessive compulsive disorders. Psychother Psychosom 1986;46:35-44.
  18. Fava GA, Grandi S, Canestrari R: Prodromal symptoms in panic disorde with agoraphobia. Am J Psychiatriy 1988;145:1564-1567.
  19. Schmale AH:Reactions to illness. Psychiat Clin N Am 1979;2:321-330.
  20. Pilowsky I: Abnormal illness behavior. Psychother Psychosom 1986;46:76-84.
  21. Engel GL: The biopsychosocial model and the education of heatlh professionals. Ann NY Acad Sci 1978:310:169-181.

A pituitary tumor survivors perspective:

Originally presented as an address by Robert Knutzen at the Pituitary Awareness Days at the University of Virginia, May 26-27, 1995.

Both in medical literature and anecdotally, we find clear and unmistakable links between sexual dysfunction and pituitary problems. Hormonal/medical therapy is directed at treating sexual dysfunction. Regrettably, no consensus has been reached on how these sexual problems affect the emotional and psychological well being of patients.

The medical community in unevenly divided in its recognition of emotional and psychological factors in the lives of pituitary tumor patients in general. Usually, these emotional/psychological factors are ignored or lightly dismissed. Whereas there is general recognition that Cushings patients are often "depressed" as a result of high cortisol levels, it is presumed that the "problems" go away with a successful lowering of these levels.

As a patient, I recognize the extremely thin veneer of credibility afforded to me by the scientific and medical community, but I am prepared to risk the criticism by insisting that the issue be studied and discussed in depth. Even among our scientific advisors, the opinions are nearly 180 degrees apart, except on Cushing's depression where near unanimity reigns.

At the risk of alienating some in the medical community, however I am prepared to hide behind the skirts and opinions of Dr. Robert Gagel of the University of Texas, who reports that hyperprolactinoma patients struggle with most severe and difficult psychological issues.

Also, Dr. Louis Sobrinho of Portugal conducted studies which led him to conclude that a high percentage of hyperprolactinemic women were daughters of abusive, absent or alcoholic fathers.

According to Dr. Anne Klibanski, studies along these lines are currently ongoing at Harvard University.

At my suggestion, my friend and personal physician Dr. Shereen Ezzat at the University of Toronto conducted a survey and interviews with the help of a clinical psychologist and wrote "Living with Acromegaly" for the September 1992 issue of "Endocrinology and Metabolism Clinics of North America."

He says, among other things, "extremely little, however, has appeared in the literature about mental and emotional attitudes in patients with acromegaly....The incidence and severity of psychopathology associated with acromegaly are still largely undocumented. It has been suggested, however, that the disorder may be commonly associated with psychosocial disturbances."

He also writes, "hyperprolactinemic patients with amenorrhea have been reported to have a greater frequency of depression, hostility and anxiety than normal prolactinomic controls."

Of the 3 male and female acromegalic patients surveyed, the majority of female patients, but only half of male patients, reported significant reduction in sexual desire or enjoyment.

Three-quarters of the acromegalic patients indicated that their personality was altered by their medical condition.

Again from Europe, Dr. Giovanni Fava, editor in chief of "Psychotherapy and Psychosomatics," published by S. Karger AG, Basil, Switzerland, regularly sends us his group's findings. In one of his most recent articles he writes, "an impressive body of knowledge has accumulated on the relationship of endocrine disease to psychological distress, or endocrine dysfunction in psychiatric illness, notably depression, and on the limbic-hypothalamic control of hormone function."

On the other hand, the role of stressful life events which may increase vulnerability to endocrine disorders has been largely neglected,

In discussions with many hundreds of patients in North America, Europe an Australia, I will unequivocally state that our problems go far deeper than two inches behind the eyes.

Superb surgical skills and skillful, sensitive medical attention in and of itself, in many patients, is not sufficient for recovery.

Particularly, those of is with secreting tumors find it extremely difficult to "balance out" and return to whatever passes for normal.

A great number of us do not remember what normal is or was and struggle with emotional issues which are almost solely controlled by the pituitary/ hormonal functions. It is clear that the old adage "mind over matter" holds true for many. However, mind over hormone is an entirely different issue, requiring skills, medicines and consideration previously not given to pituitary patients.

We hope that discussions today will open the way to more research and better care for pituitary patients in this area.

The need exists to classify, understand, and name the sexual, emotional and psychological problems we struggle with, without stigmatizing ourselves in the eyes of our insurers, the public at large, or our own families.

The failure of so many pituitary patients to readjust to family, social and work relationships after surgery and medical care is alarming. It is clear to a growing number of us that some extra steps are required on the ladder to recovery. Our challenge to endocrinologists, neurosurgeons, radiologists and others is to consider the first step, for free. Gather systematic data in a meaningful format, agreed upon amongst you, regarding the psychosocial adjustment made or faced by patients post medical , surgical treatment. In two years, let's examine the data and take the next steps.

Most of us are neither lazy, indifferent or ungrateful for skillful care and intervention. We are just not emotionally cured.

Whereas with other chronic, life-threatening or life-altering illnesses have an inner tool kit available to help them cope, adjust and repair the emotional and psychological damage, I would argue that those of us with pituitary tumors have had hand grenades thrown in out tool kits.

We need new tools. Hopefully, by working together, we can create them.

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