The Symptoms Of Depression In Endocrine
By Burton Hutto, M.D.
University of North Carolina School of Medicine in Chapel Hill
Many endocrine disorders present with symptoms of depression, thus differentiating primary depressive
disorders from such endocrine conditions can be challenging. Awareness of the typical clinical picture
of endocrine disorders is of primary importance. This article discusses a variety of common and uncom-
mon endocrine disorders and the symptomatology that might suggest a depressive illness and reviews
literature on how endocrinopathies can mimic depression. Emphasis is also placed on the role that
stress can play in the pathogenesis of endocrine disorders. Psychiatrists should be familiar it with the
range of presenting symptoms for endocrine disorders and they should not rely on the presence or
absence of stressors to guide their differential diagnosis between depression and endocrine disorders.
NS Spectrums 1999;4(4):51-61
INTRODUCTION and the endocrine system, several interactions
have been described. For example, depression is
The close relationship of psychiatry and endocrinol- characterized by typical alterations of endocrine
ogy was recognized many years ago by many great functioning. Specically, there are reproducible
psychiatrists, including Sigmund Freud, who wrote ndings of changes in the hypothalamic-pituitary-
the following in 19231: adrenal axis and the hypolhalamic-pituitary-thyroid
axis. Not only may such endocrine changes result
“From a clinical standpoint the neuroses must from depression, but they may be central to the
necessarily be put alongside the intoxications and pathogenesis of depression. Also, endocrine
such disorders as Graves’ disease. These are disorders may routinely lead to depressive
conditions arising from an excess or a relative syndromes, either in the same ways that other
lack of certain highly active substances, whether physical illnesses can lead to depression through
produced inside the body or introduced into it psychological reactions to stress or through
from outside-in short. they are disturbances of the particular biological mechanisms related to the
chemistry of the body, toxic conditions. If someone endocrine system’s role in the stress response.
succeeded in isolating and demonstrating the Psychological and psychiatric factors also may play
hypothetical substance or substances concerned a role in the pathogenesis of endocrine disease.
in neuroses, he would have no need to worry about In addition, given an overlap of symptomatology,
opposition from the medical profession. For the the differential diagnosis of depression and certain
present, however, no such avenue of approach to endocrine diseases may be complex. Depression
the problem is open.” in the context of endocrine disease or dysfunction
may be more difcult to treat or may respond only
Today, research has shown that the relationship of when the endocrine disorder is addressed. Also,
some psychiatric illnesses to endocrine disorders the course of endocrine disease may be adversely
may be much greater than the similarity Freud affected by depression. Conversely, the course
suggested. Researchers have developed vast of depression might favorably be altered by the
fruitful areas of investigation on the many types therapeutic use of hormones. There are likely
of interactions between the endocrine system and many other areas of interaction, some as yet
the central nervous system. Regarding depression undiscovered.
This review focuses primarily on the psychological stood that hypothyroidism is commonly accompa-
and psychiatric factors that may play a role in nied by psychiatric symptoms such as depression,
the pathogenesis of endocrine disease, and the anxiety, and cognitive impairment. Recently it
complexities involved in the differential diagnosis has become clear that psychiatric symptoms may
of depression and certain endocrine disorders. frequently precede the onset of other recognizable
With the intent of informing clinical psychiatrists signs or symptoms of hypothyroidism.2 Typical
about the possibility of endocrine disease in symptoms, such as fatigue, decreased memory,
depressed patients, I describe the similarities and and weight gain, might lead the clinician to the
discriminating features between depression and a diagnosis of primary psychiatric illness. Most
range of endocrine diseases that could be mistaken psychiatrists who are not attentive to this fact
for depression at rst, or even second, glance. or who omit a thorough review of systems could
miss the typical distinctive symptoms and signs of
Considering psychiatrists’ tendency to search hypothyroidism, such as cold intolerance, husky
for the meaning of symptoms, this review also voice, constipation, menorrhagia, and muscle
highlights research that has demonstrated that life cramps. Without a thorough physical examination,
events and psychological factors might contribute distinctive signs of hypothyroidism such as dry,
to the pathogenesis of some endocrine disorders. coarse skin, mild edema, bradycardia, or goiter
The relationship of these psychologically meaning- might easily be overlooked.
ful environmental factors to the development of
illness may be understood as a psychosomatic Although these considerations suggest that the
relationship. Most research does not suggest that diagnosis of hypothyroidism may be missed very
any specic meaning or conict contributes to the easily, the rate of such misdiagnosis is unknown.
pathogenesis of endocrine diseases, but there is In an attempt to evaluate the prevalence of thyroid
good evidence that psychologically meaningful abnormalities in depressed outpatients, Fava et al3
environmental factors contribute to the etiology of found no cases of hypothyroidism or hyperthyroid-
some cases of endocrine disease. ism in 200 patients. Although they concluded
that thyroid disease is extremely uncommon in
The matter of differential diagnosis is compounded depressed outpatients, it is difcult to generalize
by the realities of clinical psychiatry. In the attempt from this recruited population to a clinical popula-
to become more efcient, psychiatrists have been tion that would also include inpatients. In any
led to abbreviate evaluations and to limit laboratory case, this most well-known endocrinopathy is
investigation. Psychiatrists have traditionally omitted routinely considered a diagnostic possibility by
a complete physical examination in outpatients, most psychiatrists, especially in young women. It
and few psychiatrists perform an adequate review is indisputable that a thyroid-stimulating hormone
of systems. Since only patients admitted to a (TSH) level is strongly indicated in cases of
psychiatric hospital are likely to receive the most treatment-resistant depression.4
thorough evaluation, outpatients are especially
vulnerable to misdiagnosis by psychiatrists of Iatrogenic hypothyroid states may contribute to
medical illness as psychiatric illness. Now that only suboptimal recovery from depression. In particular,
the most dangerously ill psychiatric patients ever the effects of lithium on thyroid hormone biosyn-
gain admission, and thus a complete evaluation, thesis and release can lead to a hypothyroid state.
this vulnerability of outpatients has grown. The Thus, patients on lithium should have TSH levels
missed diagnosis of endocrine disease in patients assayed twice yearly. As another example, the
presenting with depressive symptoms seems rapid withdrawal of thyroid supplements used as
especially likely. augmentation for treatment of mood disorders can
also induce a hypothyroid state. To illustrate this
THYROID DISORDERS possibility, one study of patients whose thyroid
replacement after thyroidectomy was withdrawn
Hypothyroidism found that such patients who had a history of mood
disorders were more likely than those without a
For more than 100 years, physicians have under- history of mood disorders to experience mood
changes after discontinuation of their thyroid Psychiatric Rating Scale, researchers found no
replacement.5 difference between the groups in current mood
disorder. However, they did nd in the subclinical
The diagnosis of subclinical hypothyroidism is hypothyroidism group an impairment of logical
even more elusive and has a more controversial memory that improved with treatment using
relationship to depression. When hypothyroidism levothyroxine. The authors suggested that the
is graded based on laboratory data, elevated perception of illness may be a confounding factor
TSH levels an decreased thyroid hormone levels in comparing subclinical hypothyroid patients with
are known as grade I hypothyroidism. Grade II patients who have no thyroid pathology. Thus,
hypothyroidism is, diagnosed by elevated TSH having grade II hypothyroidism did not appear to
levels with normal thyroid hormone levels. Grade produce symptoms of mood disorder other than
III hypothyroidism presents with normal or high- cognitive impairment at the time of the illness.
normal TSH levels, but an exaggerated response However, this cross-sectional approach is difcult
of TSH to thyrotropin-releasing hormone (TRH) in to compare with the studies of longitudinal course
the TRH stimulation test. previously described.
This review thus far has centered on grade I Except for the one nding that memory impairment
hypothyroidism, which typically presents with the in grade II hypothyroidism can be treated with
well-known signs and symptoms. The diagnoses levothyroxine,12 no study thus far has demonstrated
of grade II and III hypothyroidism, which are made that treatment of grade II or III hypothyroidism
by laboratory evaluation, may present with few, if affects the course of depression. Fava et al3 found
any, nonpsychiatric signs or symptoms.6 These no relationship between response of depression
diagnoses have an unclear prevalence. They may to fluoxetine and any thyroid measure. They
occur in 5% to 10% of the general but rates of concluded that the presence of subtle thyroid
grade II hypothyroidism in depressed populations function abnormalities does not have an impact on
have ranged from 2.6% to 13.7%3,8,9 treatment outcome. Since specic interventions
in grade II or III hypothyroidism are not known to
Some investigations of the relationship of grade II or give clear benet for depressive symptoms, the
III (subclinical) hypothyroidism to depression have need for testing to diagnose this condition could be
suggested that subclinical hypothyroidism is addi- questioned at this time.
tive with other risk factors for patients predisposed
to depression. One study of 148 general medical Antithyroid antibodies have provided another
patients found a history of treatment for depression area of investigation in the interaction of thyroid
in 50% of those with TSH values >3 IU compared disease and depression. It has been hoped that
with only 18% of those with values <3 IU10. Another these antibodies could be used as a screen for
study evaluated 31 patients who, based on personal grade III subclinical hypothyroidism, but there is
or family history, were at risk for thyroid illness.11 no clear association between being positive for the
antibodies and depression.13
By interviewing the patients before their thyroid
functions were assessed, this study found a 56% However, the presence of antithyroid peroxidase
lifetime prevalence of depression in those who had antibodies does seem to be closely related to
subclinical hypothyroidism compared with an 18% postpartum thyroiditis. This condition is character-
prevalence in the euthyroid patients. ized by a typical course of hyperthyroidism about
14 weeks postpartum, followed by hypothyroidism
In contrast, other investigators have suggested that at about 19 weeks. In a large study of this condi-
subclinical hypothyroidism does not signicantly tion comparing antibody-positive and antibodynega-
affect mood or functioning. One recent study tive groups, patients in the antibodypositive
compared patients who had subclinical hypothyroid- group had more symptoms of depression by 4
ism with euthyroid patients who had goiter, to control weeks postpartum, long before thyroid symptoms
for the perception of illness.12 Using the Hamilton emerged.14 Patients who were antibody-positive
Ratings for Depression and Anxiety and the Brief generally had more symptoms of depression, and
their symptoms occurred before, during, and after with Graves’ disease (the most common cause of
overt thyroid dysfunction as well as when no other hyperthyroidism) with 372 selected and matched
thyroid abnormalities were found. However, there controls, it found signicantly more negative life
are no data on whether any specic intervention events and higher negative life event scores in
would be beneficial15; thus, it could be argued the Graves’ disease patients during the 12 months
that testing for the condition is unnecessary at preceding the diagnosis.18 This nding suggests
this time. that stress may play some role in the etiology of
hyperthyroidism, and it illustrates that reliance on
Although it is clear that grade I hypothyroidism the patient’s report of recent stressors as a means
must be diagnosed and treated, the importance to distinguish between psychiatric illness and
of further evaluation or treatment of antithyroid hyperthyroidism might often lead to error.
antibodies and grade II or III hypothyroidism in
depression is less clear. Associations appear to The standard method for conrming (if not discover-
exist between antithyroid antibodies and grade ing) the diagnosis of hyperthyroidism is through
II and III hypothyroidism and depression, but the laboratory testing. The nding of a low TSH level
causal relationships and the role of treatment need is suggestive of hyperthyroidism, but the diagnosis
further evaluation. requires the nding of elevations in thyroid hormone
levels. 19 A low TSH should be repeated along
Hyperthyroidism with thyroid function tests. Although standard
thyroid function tests typically assay total thyroxine
Hyperthyroidism frequently presents initially with (T4), triiodothyronine (T3) resin uptake, and free
depressive symptoms.16,17 Because hyperthyroidism T4 index (a derived value), some patients have
produces such symptoms as anxiety, fatigue, hyperthyroidisin based on elevated levels of free
insomnia, mood lability, decreased concentration, T3, known as T3 thyrotoxicosis, which is typically
and decreased memory, a clinician might easily associated with a thyroid nodule. Thus, assays
entertain the diagnosis of major depression. A of free T 3 may be indicated in some cases of
thorough review of systems might prevent such suspected hyperthyroidism.
a misdiagnosis by uncovering heat intolerance,
increased appetite accompanied by weight loss, Because transient and clinically questionable
diaphoresis, diarrhea, palpitations, proximal muscle elevations of thyroid hormone levels have been
weakness, and warm skin. On physical examina- reported in psychiatric populations, especially at the
tion, one might even note a goiter, the characteristic height of illness or at the time of hospitalization,20,21
proptosis, an impaired upward gaze, or a tremor the possibility of false-positive results from labora-
as further evidence of the illness. tory testing makes diagnosis of hyperthyroidism
especially difficult in psychiatric populations.
It can be tempting to rely on the presence or Elevations on thyroid function tests in psychiatric
absence of psychological stressors expected to patients with no clear nonpsychiatric signs or
accompany the onset of depression as a means to symptoms of hyperthyroidism should be followed
rule out primary medical illness as the etiology of with repeat testing in 2 weeks.
new psychiatric symptoms. However, the presence
of stressors can often be incidental in the presenta- ADRENAL DISORDERS
tion of any illness. In addition, many physical
illnesses including hyperthyroidism develop in the Hypercortisolemia or Cushing’s
context of stressful life circumstances. Although Syndrome
hyperthyroidism was once considered a prototype
of psychosomatic illness, that view has been mostly Cushing’s disease refers to a pituitary tumor that
unsupported by research, in that no specic conict secretes adrenocorticotropic hormone (ACTH),
or psychological variable appears correlated to thus stimulating cortisol secretion. Cushing’s
hyperthyroidism. On the other hand, hyperthyroid- disease is the most common cause of noniatrogenic
ism may involve a response to stress. When one Cushing’s syndrome, the condition related to
recent study compared self-reports of 208 patients elevated circulating corticosteriods. Although
Cushing’s syndrome can routinely present with decreased libido, and sleep disturbance, which all
various psychiatric symptoms,16,22,23 depression suggest major depression, are the most disruptive
occurs in about half or more of these patients.24,21 symptoms they experience with the illness. Thus,
these patients would often present with prominent
Some signs and symptoms of Cushing’s syndrome, symptoms of depression.
such as obesity, hypertension, acne, hirsutism, and
hyperglycemia, are each prevalent problems, so the Some authors classify the depression typically
evaluating clinician might never consider Cushing’s found in Cushing’s syndrome as atypical instead
syndrome. There is no pathognomonic nding for of melancholic.31 However, this emphasis on mood
Cushing’s syndrome, but a cluster of signs and reactivity and weight gain in contrast to anhedonia
symptoms should trigger further investigation. Of and weight loss has been questioned by others.23
the numerous signs and symptoms of Cushing’s
syndrome, central obesity, ecchymoses, plethora, Accurate and early diagnosis of Cushing’s syndrome
proximal muscle weakness, osteopenia, hypertension, requires a high degree of suspicion given the
and white blood cell count greater than11,000/mm3 prominence of depressive symptoms and the
have been shown to be good discriminant indices for frequency of stressors typically associated with
the presence of Cushing’s syndrome.26 If suspected, the onset of depression. With treatment for the
the svndrome can be evaluated further with an underlying cause of the hypercortisolemia, many
11:00 pm cortisol check and 24-hour urine test patients will have a remission of their depression.22
for 17-hydroxycorticosteriods.27 Further laboratory However, the recovery may be slow or incomplete.32
work-up of suspected Cushing’s syndrome might Cushing’s disease, like depression, is also more
necessitate consultation with an endocrinologist. Even common in women. Patients with depressive
the corticotropin-releasing factor stimulation test yields symptoms who do not respond well to standard
ambiguous results in differentiating depression and treatment should be carefully screened for signs
Cushing’s syndrome in questionable cases.17,28 and symptoms of Cushing’s syndrome.
As with hyperthyroidism, stressful life events can be Adrenal Insufciency
incidental or perhaps causative with many illnesses,
so a history of recent stressors cannot reliably Adrenal insufficiency, also known as Addison’s
discriminate depression from other illnesses that disease, most often follows autoimmune destruc-
mimic depression. In one study of 66 Cushing’s tion of the adrenal glands, and symptoms do
syndrome patients matched by sociodemo- graphic not typically manifest until more than 90% of the
variables with 66 healthy controls, all were inter- adrenal function is lost. Early symptoms of adrenal
viewed with a structured format for stressful life insufficiency often mimic depression, including
events.29 The Cushing’s syndrome patients reported weakness, fatigue, weight loss, and anorexia.‘Since
more losses and undesirable and uncontrolled typical physical symptoms such as hypotension,
events than the controls. The stressors appeared nausea, and vomiting also simultaneously herald
to be causal for the Cushing’s disease patients the onset of adrenal insufciency, many patients
specically, and there were no differences between would not present initially to a psychiatrist. Although
patients with and without depression. hyperpigmentation is pathognomonic of Addison’s
disease, it does not occur in cases of secondary
Many Cushing’s syndrome patients are, in fact, adrenal insufciency, which is caused by decreased
treated for psychiatric disorders before their corticotropin (ie, ACTH), since excess melanin
illness is diagnosed. In one study, 7 of 44 patients production in hyperpigmentation is stimulated by
(17%) were hospitalized as psychiatric patients the elevated ACTH in adrenal failure.
before the diagnosis of Cushing’s syndrome was
made, and one reported case had even received PARATHYROID DISORDERS
electroconvulsive therapy. 30 This same study
found that Cushing’s syndrome patients report Hyperparathyroidism
that the symptoms of fatigue, weight gain, mood
lability, impaired concentration, depressed mood, Hyperparathyroidism, an elevation of parathyroid
hormone most commonly caused by a benign leads to hypocalcemia, which, in turn, can cause
adenoma, produces hypercalcemia. Hypercalcemia severe symptoms of central nervous system
from any cause often leads to a variety of medical disturbance, such as tetany or seizures. In some
problems, including psychiatric symptoms. Although cases, more subtle psychiatric symptoms can
very high calcium levels can cause prominent precede these more prototypical symptoms.39 More
confusion or delirium, more moderately elevated subtle psychiatric symptoms such as depression,
calcium levels can induce depression, decreased irritability, and anxiety may be characteristic of
concentration and memory, and fatigue. Such the illness.40
depressive symptoms are common initial complaints
for patients with hyperparathyroidism.34 Even mildly Despite the possibility of depressive symptoms,
elevated calcium levels <12 mg/dl may produce this endocrinopathy would rarely be of concern to
signicant psychiatric symptoms that resolve when psychiatrists except for the following associated
the calcium level is decreased.35 Other physical issues. In addition to psychiatric manifestations
symptoms of hypercalcemia such as anorexia of hypoparathyroidism, the psychiatrist should
or muscular weakness can also be mistaken as note that the illness can produce extrapyramidal
psychiatric complaints. The depressive symptoms syndromes, and patients with such syndromes can
can so dominate the clinical picture that patients be sensitive to medications that cause Parkinsonian
can be psychiatrically hospitalized,36 and there have symptoms. A second concern for psychiatrists is
been reports of suicide attributed to hyperparathy- that, since magnesium is required for the release
roidism.37 of parathyroid hormone, decreased magnesium
levels is one of the causes of hypoparathyroidism.
As with other endocrine diseases such as hypothy- Hypomagnesemia itself can have additional
roidism, hyperthyroidism, or Cushing’s syndrome, neuropsychiatric symptoms such as weakness,
the range of somatic complaints in hypercalcemia fatigue, and slowed cognition that could mimic
might even be interpreted as somatization in the depression.
context of a depression. The key is the recogni-
tion of a pattern of symptoms suggestive of a DIABETES MELLITUS
specic endocrinopathy. The following cluster of
symptoms has traditionally been associated with Diabetes mellitus is a disorder of insulin production
hyperparathyroidism: evidence of bone changes or (type I) or insulin receptors (type II). Although
pain (a symptom of hyperparathyroidism, but not the prominent early symptoms of fatigue, memory
hypercalcemia from other causes), renal stones, impairment, and weight loss could be attributed to
abdominal groans, psychic moans, and fatigue a depressive disorder, the metabolic toll taken by
overtones.38 (Note that the italicized terms rhyme, diabetes becomes increasingly difcult to overlook
to aid in remembering this symptom cluster.) Other as other symptoms such as polyuria, polyphagia,
common symptoms and associated conditions extreme weakness, and infection develop. This
include polydipsia, polyuria, nocturia, constipation, condition of hyperglycemia is also frequently
nausea, heartburn, and pruritis. detected by simple screening of serum chemistry
Because the laboratory investigation of hypercalce-
mia can yield false-negatives, serial determinations In contrast with other endocrine diseases that
of calcium levels or correlation of calcium levels mimic depression or contribute to depression
with parathyroid hormone levels are often required through shared biological underpinnings, diabetes
to detect true hyperparathyroidism, especially if it appears to relate to depression mostly in the way
is mild. It is important for psychiatrists to note that that any other chronic illness does. Although there
lithium use is one possible cause of hypercalcernia are suggestions that depression contributes to the
not due to hyperparathyroidism. pathogenesis of diabetes,41 the dominant clinical
issues relate to comorbidity and how depression
Hypoparathyroidism affects the course of illness42 and the quality of
life.43 Two excellent reviews discuss the range of
Hypoparathyroidism from a variety of etiologies topics involved in the psychological care of patients
with diabetes44 and the psychiatric treatment of hormone synthesized in the pituitary.
depression in these patients.45
When the tumor overproduces ACTH, this condition
DISORDERS OF REPRODUCTIVE ENDOCRI- is Cushing’s disease, previously described in the
NOLOGY section on adrenal disorders. Acromegaly is the
result of tumors that secrete growth hormone. The
Because many disorders of male reproductive amenorrhea galactorrhea syndrome in females is
endocrine function are congenital, such disorders the result of prolactinomas. Pituitary disease
presenting in adulthood would not usually exhibit can also lead to underproduction of all pituitary
psychiatric symptomatology that would directly hormones, a condition known as hypopituitarism.
lead to psychiatric evaluation. However, one recent Each of these conditions can present with depres-
study of depressed hypogonadal men showed that sive symptoms as a part of the clinical picture.
testosterone replacement might be an effective
augmentation of antidepressant medication. 46 Acromegaly
Remarkably, by simply advertising for men who had
experienced only partial response of depression Growth hormone-secreting tumors presenting
to selective serotonin reuptake inhibitors, and then before adulthood lead to the potentially distress-
assaying their testosterone levels, the authors ing symptom of gigantism, so that associated
found that 5 of 16 respondents to the ad had psychiatric symptoms would be difcult to attribute
low or lownormal testosterone levels (200 to 350 directly to the excess growth hormone. The
ng/dL; reference range 300 to 900 ng/dL). Perhaps psychiatric manifestations of the rare condition of
hypogonadism is more common in depressed men acromegaly caused by growth hormonesecreting
than previously realized. tumors in adulthood are poorly established. One
study of patients who developed acromegaly in
The often congenital disorders of female reproduc- adulthood found no increase in psychiatric morbidity
tive endocrine function also do not typically present in general and no increased incidence of depression
with prominent psychiatric symptoms. However, specically in comparison with general and patient
there are important considerations relating female populations.52 However, in an extraordinary self-
reproductive functioning to depression. Pregnancy, report by a clinician who developed acromegaly
by no means a disorder or illness, can present with early in her career, prominent psychiatric symptoms
fatigue or mild personality changes. The diagnosis preceded accurate diagnosis.53 Early symptoms
of postpartum depression is well established, and included insomnia, weight loss, fatigue, and anxiety.
it may be at least partially due in some cases Characteristic physical changes of acromegaly
to postpartum thyroiditis, which was discussed led to subjective body image distortions. The
above. patient was diagnosed by several physicians
as depressed, stressed, psychosomatic, sinus
Menopause also is not an illness, but patients infected, suffering from allergies, and (despite no
can present during this expected transition with laboratory abnormalities) possibly hypothyroid,
depressive symptoms. Complex interrelationships diabetic, or infected with a sexually transmitted
between the typical hormonal changes, the common disease. Her marriage and other relationships
psychological changes, and mood changes during deteriorated. The accurate diagnosis was made
menopause are incompletely understood as serendipitously by a sinus film. Obviously, the
well as controversial. 47-50 One very clinically diagnosis can be elusive, and it can present with
relevant problem in the context of menopause is prominent depressive symptoms.
the underdiagnosis of major depression, which
contributes to undertreatment of depressive Prolactinoma
symptoms attributed to menopause.51
Most evidence suggests that prolactinomas in
ANTERIOR PITUITARY women can present with hostility, anxiety, and
decreased self-esteem 54,55 that can respond to
Tumors of the pituitary can overproduce any removal of the adenoma.56 Yet, one recent study
comparing women who had hyperprolactinemia psychiatrists in inpatient and outpatient settings.
with women who had acromegaly or nonfunction- Often such presentations remarkably resemble
ing pituitary adenomas found higher anxiety, but depressive disorders. Psychiatrists should be
not more depression in the hyperprolactinemic familiar with the range of presenting symptoms
group.57 for endocrine disorders, and they should not rely
on the presence or absence of stressors to guide
A fascinating study demonstrated environmental their differential diagnosis between depression and
stressors that related to the later development endocrine disorders. Even the more psychological
of hyperprolactinemia. 58 Comparing sisters symptoms of depression such as guilt or feelings
of prolactinoma patients with normal age and of worthlessness can be found in undiagnosed
socioeconomically matched controls, 23 of 37 endocrine disorders, perhaps as secondary reac-
sisters of patients and 27 of 72 controls had tions to otherwise unexplained losses of function
experienced paternal deprivation (ie, absent or and stability. More reliable discrimination is made
violent alcoholic father before age 9 years). In by careful review of systems, targeted physical
this group of 50 women with paternal deprivation, examination, and carefully planned laboratory
12 had prolactin levels greater than 20 ng/ml, testing. Even with an adequate assessment of a
compared with 3 of the other 59 women. The depressed patient, some endocrine disorders could
authors suggested that environmental factors play a remain elusive. Specically, Cushing’s syndrome
greater role than genetic factors in these observed can present with a variety of mild-to-moderate
prolactin level elevations. subjective, physical, and laboratory changes that
would need to be recognized as a cluster of signs
As with Cushing’s disease and hyperthyroidism, and symptoms. For other endocrine disorders,
life stressors seem to precede the onset of prolac- such as disorders of reproductive endocrinology,
tinomas.59 Once again, reliance on the presence of the prevalence and characteristics of psychiatric
stressors to discriminate endocrine disorders from symptomalogy are unclear. The clinician should
depression could be misleading. initiate standard treatment in the adequately
evaluated depressed patient, and be prepared
Male patients with prolactinomas suffer a second- to explore other elusive diagnoses, including
ary bypogonadism and report decreased libido. endocrine disorders, in patients who do not respond
Since men will obviously lack the amenorrhea and as expected.
galactorrhea that bring women to medical attention
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