This is a subject seminar of neuropsychiatric manifesations of endocrine disorders.It took a lot of time to prepare,it helps fellow residents of Gen medicine to download and present as it is.

1. PRESENTOR: DR.DHEERAJ KUMAR
MODERATOR: DR.CHANDRASEKHAR
A.L
NEUROPSYCHIATRIC
MANIFESTATIONS
OF ENDOCRINE DISORDERS

2. INTRODUCTION
 It has long been known that endocrine disorders are
associated with neuropsychiatric symptoms
 In 1786, Parry described psychotic symptoms
associated with hyperthyroidism,
 Graves first lectured on the psychiatric complications
of hyperthyroidism in 1834.

3.  Psychiatric symptoms can precede or present
concurrently with the more typical physical
symptoms of endocrine disease
 These secondary disorders can be impossible to
distinguish from primary psychiatric disorders, such
as depression, mania,psychosis, anxiety, delirium, or
dementia

4.  When psychiatric symptoms are thought to be
secondary to endocrine disease, the primary
treatment focus remains correcting the endocrine
disorder.
 That being said, there are times when the psychiatric
symptoms are severe enough to warrant immediate
intervention like mania, psychosis, and severe
depression that could be life-threatening

5. THYROID DISORDERS
 HYPERTHYROIDISM (THYROTOXICOSIS)
 Numerous neuropsychiatric symptoms have been noted in
patients with hyperthyroidism and include psychosis,
depression, mania, anxiety, and cognitive dysfunction.
 These can occur with either
 primary hyperthyroidism (Graves disease)
 toxic nodular goiter or
 excessive consumption of exogenous thyroid hormone

6.  Brownlie and colleagues (2000) reported a series of
18 patients: of which
 Mania – 7 patients
 Depression – 7 patients
 Psychosis – 3 patients
 Delerium – 1 patient
 Thus the range of neuropsychiatric symptoms seen
with hyperthyroidism is quite broad.

7.  The presenting neuropsychiatric symptoms of
hyperthyroidism include
 emotional lability
 poor impulse control,
 crying spells
 euphoria
 irritability
 Distractibility
 reducedattention, impaired recall, and psychosis (delusions
and hallucinations)
 A minority of patients can present with symptoms of
depression,apathy, or lethargy

8. HYPOTHYROIDISM (MYXEDEMA)
Neuropsychiatric symptoms include:
 cognitive dysfunction,
 affective disorders, and psychosis
 The psychiatric presentation may be
indistinguishable from a primary psychiatric
disorder, thus reinforcing the importance of ruling
out medical causes of psychiatric disorders.

9.  The onset of symptoms of hypothyroidism is often
gradual, and slow progression is common, especially
in the elderly, mimicking the development of a
degenerative dementia

10.  Common symptoms include slowed comprehension
and impairment in attention, recent memory, and
abstract thinking.
 In contrast to cortical dementias such as Alzheimer’s
disease and frontotemporal degeneration, the
cognitive disorder of myxedema does not present
with discrete cortical syndromes like aphasia,
anomia, apraxia, and frontal disinhibition.

11.  The most common affective disorder seen with
hypothyroidism is depression, manifested most often
as reduced mood, psychomotor retardation, sleep
and appetite disturbances, anhedonia, reduced
libido, and emotional lability. Suicidal thinking,
delusions, and hallucinations can be present in more
advanced illness.
 hypothyroidism had a greater risk of being admitted
for the treatment of depression or bipolar disorder,
and that this risk was greatest in the first year

12.  A meta-analysis of individuals with treatment
resistant depression demonstrated that
approximately 50% had subclinical hypothyroidism,
and the response to antidepressant therapy is known
to be reduced if the thyroid disease is not treated.
 Although it is generally believed that treatment of
the underlying hypothyroidism will treat the
neuropsychiatric symptoms, Demartini et al. (2010)
found that thyroid replacement alone was not
effective in producing remission of the depressive
symptoms.

13.  Compared to depression, mania is a much less
common manifestation of hypothyroidism; however,
there are a number of reported cases of
hypothyroidism presenting with symptoms of mania
 Patients can present with elevated mood and energy,
irritability, psychomotor agitation, decreased need
for sleep, increased goal-directed behavior,
pressured speech, flight of ideas, grandiosity,
hallucinations,and delusions.

14.  Hypothyroidism has been associated with psychosis
(myxedema madness), and there is no typical
presentation of psychotic symptoms which can
include delusions (paranoia), auditory and visual
hallucinations, perseveration, and thought
disorganization
 Psychosis has been noted in 5–15% of patients with
hypothyroidism

15. ADRENAL DISORDERS
 HYPERCORTISOLEMIA (CUSHING’S SYNDROME)
 Psychiatric disturbances are common with Cushing’s
syndrome.
 major depression was on average 57%, with a range of 50–
80% across studies
 Patients with depression appeared to have a more
severe clinical presentation and have higher cortisol
levels than patients with increased cortisol without
depression.

16.  Mania in Cushing’s syndrome presents less
commonly than depression, though approximately
30% of patients present with hypomanic or manic
symptoms, subclinical mood fluctuations being more
common.
 Hypomania or mania may be some of the earliest
signs of illness onset

17.  Anxiety can be commonly associated with Cushing’s
syndrome.
 The rate of generalized anxiety disorder has been
noted to be as high as 79%, and panic disorder as
high as 53%.
 Cognitive dysfunction has been noted in
approximately two-thirds of patients with Cushing’s
syndrome. The major impairments seen are :
 nonverbal, visual-ideational, visual-memory, and spatial-
constructional abilities

18.  MANAGEMENT:
 Although the successful control of hypercortisolism
can result in a progressive improvement of
psychiatric symptoms and cognitive function, this is
not always the case; Pereira et al. (2010) describe a
Cushing’s syndrome cohort comprising 33 patients,
with 67% having significant psychopathology
(primarily depression) Of which After cure of
Cushing’s syndrome,the prevalence of diagnosed
psychopathology was

19.  54% at three months,
 36% at six months, and
 24% at one year.
 They also report a 74-patient cohort that continued
to experience impairments in memory and executive
function despite long-term cure of the Cushing’s
disease.
 Thus they required treatment with antidepressants
though the primary disease is taken care of.

20. ADRENAL INSUFFICIENCY (ADDISON’S
DISEASE)
 Addison’s disease, which results in deficiencies in
glucocorticoids and mineralocorticoids
 Mild disturbances in mood, motivation, and
behavior were described as core clinical symptoms.
 Psychosis and extensive cognitive changes,
including delirium, were less common and
associated with more severe disease.
 Catatonia and self-mutilation were still more rarely
seen

21.  Adrenal insufficiency is generally treated by
replacing hydrocortisone.
 Thomsen et al. (2006) note that patients with
adrenal insufficiency may be at risk for developing
severe affective disorders, and in particular may be
at risk for developing elevated mood symptoms in
the context of receiving hormone replacement.

22. HYPERPITUITARISM
 The most common type of pituitary tumor is a
 prolactin-secreting adenoma (prolactinoma).
 Hyperprolactinemia can result in a wide variety of
symptoms, including galactorrhea, gynecomastia,
amenorrhea, decreased libido, and sexual dysfunction
 Categories of drugs associated with inducing
hyperprolactinemia include
 antipsychotics (phenothiazines, butyrophenones, and
risperidone),
 antidepressants (amitriptyline, imipramine, amoxapine),
and
 dopamine-receptor antagonists (metoclopramide,
domperidone, sulpiride).

23.  Of the atypical neuroleptics, risperidone has the
greatest capacity for stimulating prolactin secretion
 As a class, however, the atypical neuroleptics have
less tendency to be associated with increased serum
prolactin than the typical agents
 A common clinical dilemma is the psychotic patient
 on a neuroleptic drug who develops menstrual
dysfunction, galactorrhea, or
 gynecomastia (in males) associatedwith an elevated
serum prolactin concentration

24.  Treatment requires a careful balancing between the
decreasing prolactin and maintenance of adequate
control of the psychotic disorder. In such cases, it is
reasonable to consider a
 switch to an alternative antipsychotic, such as quetiapine
or
 Olanzapine which is less likely to exacerbate
hyperprolactinemia
 Consideration could also be given to the use of
aripiprazole, which might actually decrease prolactin due
to its mixed dopaminergic antagonism and agonism.

25.  If the serum prolactin level returns to normal when
the offending agent is stopped, the possibility of a
pituitary tumor is virtually excluded.
 The use of a dopamine agonist such as bromocriptine
or cabergoline is potentially risky, as these may
theoretically—though rarely—lead to worsened
psychotic symptoms despite the patient’s remaining
on an antipsychotic.

26.  Acromegaly is the clinical syndrome that results
from sustained hypersecretion of growth hormone,
most often the result of a pituitary adenoma
depression, pathological gambling, psychosis,
amotivational syndrome , harm avoidance,
neurosis,anticipatory worry, pessimism, and reduced
impulsivity and less novelty-seeking behaviors

27.  A relatively recent examination of acromegalic
patientsrevealed “increased lifetime rates of affective
disorders,”especially major depression and
dysthymia, but not anxietydisorders, which persisted
even after curative surgery.

28.  One pharmacological intervention, octreotide, has
very few psychiatric side effects, although according
to the package insert it may cause depressive
symptoms in 1–4% of patients
 In fewer than 1% of patients, may cause anxiety,
decreased libido , paranoia, or amnesia

29.  The infundibular-hypothalamic anatomy is relatively
fragile, especially traumatic brain injury(TBI),
subarachnoid hemorrhage, or brain tumors increase
 The risk of patients’ developing hypopituitarism,
including the first and most common sign of
pituitary impairment,growth hormone deficiency

30.  Regardless of etiology, the primary issue is the
decreased hormonal output, and use of psychotropic
agents directed at the nature of the presenting
symptom (e.g., antidepressantsfor depression,
anxiolytics for anxiety, or antipsychotics for
psychosis) is suggested only after correction of the
endocrine abnormality.

31.  Others describe-
 amotivation, dysphoria, disturbed sleep pattern,
 personality change, affective blunting, and auditory
 visual hallucinations
 cognitive impairment, including visual and verbal
memory impairment
 decreased quality of life (Battisetty, 2008)

32.  In one study,
 nearly half of patients with post-traumatic
hypopituitarism
 (as measured by hormone-level output) expressed
symptoms
 of mild to moderate depression, and scales reflecting
somatization
 and paranoid ideation were inversely correlated with
 pituitary hormone levels.

33. MANAGEMENT
 Many neuropsychiatric symptoms
significantly improved with hormone replacement

34. DISORDERS OF GLUCOSE METABOLISM
 DIABETES MELLITUS
 It is generally acknowledged that the presence of
psychiatric illness in the context of diabetes mellitus
can affect patient motivation and compliance with
treatment recommendations.

35.  As such, psychiatric comorbidity is associated with
decreased quality of life, increased cost of care,
elevated glycosylated hemoglobin (HbA1c), and
greater end organ damage

36. Diabetes Mellitus and Depression
 Depression is nearly twice as common in individuals
with diabetes as in those without.
 Having diabetes may increase one’s risk of
developing depression, and having depression may
increase the likelihoodof developing diabetes,
especially type II diabetes

37.  The risk of developing diabetes appears to be
greatest when the preexisting depression is non-
severe, persistent,and untreated.
 The association involves both health-related
behavior and physiological abnormalities in the
hypothalamic-pituitary-adrenal & sympathoadrenal
systems that increase insulin resistance

38.  Successful detection& treatment of depression may
prevent the development of type II diabetes in
patients at risk.
 Treatment of depression in diabetics is much the
same as in non-diabetics, though one must be aware
that antidepressants may affect appetite and blood
glucose.
 Likewise, once depressive symptoms are treated, the
patient may reengage in physical activity, which may
further influence glycemic control.

39.  The selective serotonin-reuptake inhibitors (SSRIs)
are the preferred treatment for depression in
diabetics due to their lack of effect on glucose
metabolism, lower incidence of weight gain and
carbohydrate craving, as well as the lower,but not
absent, risk of anticholinergic and cardiac side
effects

40.  However, SSRIs can suppress appetite,enhance
insulin sensitivity, and lead to hypoglycemia if diet
and medication (oral hypoglycemics, insulin) are not
adjusted accordingly.
 Tricyclic antidepressants should be avoided in the
treatment of depression in patients with diabetes, as
studies show a correlation with impaired fasting
glucose as well as increased appetite and
carbohydrate craving

41.  Treatment for diabetes in light of mental illness
should be considered carefully, recognizing that
cognitive disorders and symptoms of depression,
including low motivation andsuicidal ideation, may
affect a patient’s ability and willingness to comply
with recommendations.
 Likewise, patients with diabetes are at greater risk
for suicide than the general population, raising the
question about the safety of insulin or oral
hypoglycemics for disease management.

42.  Among antidiabetic agents used with lethal intent,
sulfonylureas were responsible for the greatest
number of deaths, though this may be related to the
larger type II population,rather than to greater
lethality. Medications should be monitored carefully
in depressed diabetics, and some studies suggest
discontinuation of insulin pumps during acute
episodesof depression with suicidal ideation

43. Diabetes Mellitus and Anxiety
 The prevalence of anxiety disorders, specifically
generalized anxiety disorder (GAD), in diabetics is
two to three times that in non-diabetics
 As with depression, the presence of comorbid anxiety
and diabetes mellitus is associated with elevated
HbA1c levels
 It is important to note that the symptoms of anxiety
disorders and depressive disorders often overlap,
making a very distinct differentiation quite difficult.
In most cases, though,treatment is very similar.

44.  Risk factors associated with more severe anxiety in
diabetics include:
1. female gender,
2. presence of diabetes complications,
3. insulin use, unemployment, smoking, and
past/presentmisuse of alcohol.

45. Protective factors include:
1. older age,
2. structured medical care, private medical insurance,
and
3. patient perception of adequate glycemic control

46.  Caution, however, should be used with
pharmacotherapy, such as benzodiazepines and beta
blockers, as they may mask the physiological
symptoms of hypoglycemia, including tachycardia

47.  Studies suggest selective serotonin reuptake
inhibitors are used with greatest frequency, owing to
their potential synergistic effects they have been
found to provide adequate control of mood and
anxiety symptoms while also improving diabetes
self-care

48. Diabetes, Eating Disorders, and Eating
Disordered Behavior
 Many studies have shown that diabetics engaging in
eating disordered behaviors, particularly insulin
omission or underuse,are at particularly elevated risk
of experiencing physical complications of diabetes

49.  Treatment of eating disorders
using a team approach, including physicians,
diabetes educators, nutritionists, and therapists

50. Diabetes Mellitus and Cognitive Changes
 Many studies have shown an association between
diabetes, both type I and type II, and the presence of
cognitive decline
 The exact cause of these cognitive changes remains
unclear, and some studies have failed to reveal an
association with HbA1c.

51.  In addition, it is thought that a state of
hyperinsulinemia, seen in type II diabetics, may
contribute to microvascular damage and may
interfere with amyloid precursor protein
metabolism, leading to cerebral beta amyloid
deposits.

52. HYPOGLYCEMIA
 Symptoms of hypoglycemia may be broken down
into two distinct constellations
 Autonomic
 Neuroglycopenic

53.  The autonomic effects are typically defined as
adrenergic or catecholamine-mediated symptoms,
including
 tachycardia,
 diaphoresis, tremor, weakness, hunger, irritability,
 Palpitations
these hyperadrenergic symptoms can mimic a panic
attack.

54.  An inadequate supply of glucose to
 the central nervous system (CNS), or
neuroglycopenia, may
 result in faintness, headache, blurred vision,
lethargy, confusion,
 dizziness, weakness, incoordination, bizarre
reversible focal neurological findings, seizures, and
coma,
 which typically abates with normalization of glucose
levels

55.  The differential diagnosis of fasting hypoglycemia
must include surreptitious administration of either
insulin or an oral hypoglycemic agent
 Factitious hypoglycemia secondary to one of these
agents must be considered prior to pancreatic
exploration for an islet cell tumor in any patient with
hyperinsulinism.

56.  The presence of anti-insulin antibodies or low C-
peptide levels at the time of hypoglycemia strongly
suggests a factitious etiology
 Screening of urine or blood for sulfonylureas
is available for patients suspected of surreptitious
oral hypoglycemic-agent ingestion.

57.  An important issue in the psychopharmacological
management of patients with hypoglycemia is the
risk of beta-blocker therapy

58.  Early misdiagnosis of hypoglycemia as
 an anxiety disorder and treatment with agents whose
action
 blocks the normal response to hypoglycemia may
prevent
 the subjective experience of potentially lethal
hypoglycemia

59.  Additionally, there is some suggestion that the use of
antidepressants can impair glycemic control leading
to hyperglycemia or hypoglycemia (Khoza, 2011),
 So serum glucose levels should be monitored more
closely if any medication is added

60. DEVIATIONS IN GONADAL HORMONES
 MALE HYPOGONADISM
 Male hypogonadism of any etiology may cause
significant psychological distress and impaired social
adjustment
 Low self-esteem and self-confidence and feelings of
inadequacy,isolation, and alienation are common.

61. PRE-MENSTRUAL DYSPHORIC DISORDER
 Diagnosis of PMDD requires five or more of 11
possible symptoms present during the late luteal
phase, approximately days 21–28 of the menstrual
cycle
 At least one of the five symptoms must be depressed
mood, anxiety, affective lability, or irritability

62.  Derangements and dysregulation of the serotonergic
system are the most probable causes of PMDD
 Treatment studies also support the serotonin
hypothesis of PMDD causality, as SSRIs have proven
efficacious in decreasing symptoms

63. summary
 The onset of symptoms of hypothyroidism is often
gradual and, especially in the elderly, mimics the
development of a degenerative dementia. In contrast
to cortical dementias such as Alzheimer’sdisease and
frontotemporal degeneration, the cognitive disorder
of myxedema does not present with discrete cortical
syndromes like aphasia, anomia, apraxia, and frontal
disinhibition.

64.  In Cushing’s syndrome, depression is extremely
common,and persistent elation rare.
 The majority of cases of primary
hyperparathyroidism are asymptomatic (Benge
et al., 2009).
 The diagnosis of Addison’s disease commonly is
delayed.In one cohort of 216 patients with adrenal
insufficiency,41% received a false diagnosis of a
psychiatric illness(Bleiken et al., 2010).
 Risperidone is the atypical antipsychotic most likely
tocause hyperprolactinemia.

65.  Acromegaly is associated with depression,
psychosis, and amotivational syndrome
 Those with insulin-dependent diabetes and
eating disorders frequently turn to insulin omission
or underuse as a means to prevent weight gain and to
promote weight loss.

66.  Beta-blocker therapy may prevent the normal
sympathetic response to potentially lethal
hypoglycemia in insulin-dependent diabetics.
 In Klinefelter’s syndrome, XXY, boys with
hypogonadism, cognitive and learning difficulties are
seen most often in verbal IQ scores, speech and
language acquisition and recognition, as well as in
memory

67. REFERENCES
 PSYCHIATRIC CARE OF THE MEDICAL PATIENT-
BARRY S.FOGEL & DONNA B. GREENBERG .
 HARRISONS 19th edition
 WILLIAMS TEXT BOOK OF ENDOCRINOLOGY
13TH edition