Seminar

On
Thyroid Storm
Myexedema and
Adrenal Crisis
[Subject- Medical Surgical Nursing]

1
L
BASIC PHYSIOLOGY AND ANATOMY OF THE THYROID GLAND
ANATOMY OF THE THYROID GLAND:

 The thyroid gland is located in the anterior portion of the neck in front of the trachea.
It consists of two encapsulated lateral lobes connected by a narrow isthmus.

2
  The normal thyroid gland weighs 20–25 g. The functioning unit is the lobule supplied
by a single arteriole and consists of 24–40 follicles lined with cuboidal epithelium.
 The follicle contains colloid in which thyroglobulin is stored.
 The arterial supply is rich, and extensive anastomoses occur between the main thyroid
arteries and branches of the tracheal and oesophageal arteries.
 There is an extensive lymphatic network within and around the gland. Although
 some lymph channels pass directly to the deep cervical nodes, the subcapsular plexus
drains principally to the central compartment juxtathyroid – ‘Delphian’ and
paratracheal nodes.

PHYSIOLOGY OF THE THYROID GLAND:

 The thyroid gland is a highly vascular organ, and its size is regulated by TSH from the
anterior pituitary. The thyroid gland produces and secures three hormones: thyroxine
(T4), triiodothyronine (T3), and calcitonin.
 Thyroxine and Triiodothyronine:
o Thyroxine (T4) accounts for 90% of thyroid hormone produced by the thyroid
gland. However, triiodothyronine (T3) is much more potent and has greater
metabolic effects. About 20% of circulating T3 is secreted directly by the
thyroid gland, and the remainder is obtained by peripheral conversion of T4.
o Iodine is necessary for the synthesis of both T3 and T4. These two hormones
affect metabolic rate, caloric requirements, oxygen consumption, carbohydrate
and lipid metabolism, growth and development, brain function, and other
nervous system activities.

3
 o More than 99% of thyroid hormones are bound to plasma proteins, especially
thyroxine-binding globulin synthesized by the liver. Only the unbound “free”
hormones are biologically active.
o Thyroid hormone production and release are stimulated by TSH from the
anterior pituitary gland. When circulating levels of thyroid hormone are low,
the hypothalamus releases thyrotropin-releasing hormone (TRH), which in
turn causes the anterior pituitary to release TSH. High circulating thyroid
hormone levels inhibit the secretion of both TRH from the hypothalamus and
TSH from the anterior pituitary gland.
 Calcitonin:
o Calcitonin is produced by C cells (parafollicular cells) of the thyroid gland in
response to high circulating calcium levels.
o Calcitonin inhibits the transfer of calcium from bone to blood, increases
calcium storage in bone, and increases renal excretion of calcium and
phosphorus, thereby lowering serum calcium levels.
o Calcitonin and PTH regulate calcium balance.

REGULATION OF THYROID HORMONE:

4
  Synthesis and release of thyroid hormones from the thyroid is controlled by thyroid-
stimulating hormone (TSH) from the anterior pituitary. Secretion of TSH depends
upon the level of circulating thyroid hormones and is modified in a negative feedback
manner. In hyperthyroidism, TSH production is suppressed, whereas in
hypothyroidism it is stimulated. Regulation of TSH secretion also results from the
action of thyrotrophin-releasing hormone (TRH) produced in the hypothalamus.

FUNCTIONS OF THYROID HORMONE:

The physiological effects of thyroid hormones are listed below:
 Increases the basal metabolic rate
 Depending on the metabolic status, it can induce lipolysis or lipid synthesis.
 Stimulate the metabolism of carbohydrates
 Anabolism of proteins. Thyroid hormones can also induce the catabolism of proteins
in high doses.

5
  Permissive effect on catecholamines
 In children, thyroid hormones act synergistically with growth hormones to stimulate
bone growth.
 The impact of thyroid hormone in CNS is important. During the prenatal period, it is
needed for the maturation of the brain. In adults, it can affect mood. Hyperthyroidism
can lead to hyperexcitability and irritability. Hypothyroidism can cause impaired
memory, slowed speech, and sleepiness.
 Thyroid hormone affects fertility, ovulation, and menstruation.

INVESTIGATIONS FOR THYROID ASSESSMENT:

Essential :
● Serum:
a. TSH-
TSH levels can be measured accurately down to very low serum
concentrations with an immunochemiluminometric assay. Interpretation of
deranged TSH levels depends on knowledge of the T3 and T4 values. In
the euthyroid state, T3, T4 and TSH levels will all be within the normal
range. Florid thyroid failure results in depressed T3 and T4 levels, with
gross elevation of TSH. Incipient or developing thyroid failure is
characterised by low normal values of T3 and T4 and elevation of TSH. In
toxic states, the TSH level is suppressed and undetectable (Table 50.1). T3
toxicity (with a normal T4) is a distinct entity and may only be diagnosed
by measuring T3, although a suppressed TSH in the presence of normal T4
suggests the diagnosis.
b. Serum thyroid hormone levels (T3 and T4)- levels are checked when TSH
abnormal
c. Thyroid autoantibodies-
Serum levels of antibodies against thyroid peroxidase (TPO) and
thyroglobulin are useful in determining the cause of thyroid dysfunction
and swellings. Autoimmune thyroiditis may be associated with thyroid
toxicity, failure or euthyroid goitre. Levels above 25 units/mL for TPO
antibody and titres of greater than 1:100 for antithyroglobulin are
considered significant, although a proportion of patients with histological
evidence of lymphocytic (autoimmune) thyroiditis are seronegative. The
presence of antithyroglobulin antibody interferes with assays of serum
thyroglobulin, with implications for follow-up of thyroid cancers. TSH
receptor antibodies (TSH-Rab or TRAB) are often present in Graves’
disease. They are largely produced within the thyroid itself.

6
● FNAC :
Fine-needle aspiration cytology (FNAC) is the investigation of choice in discrete
thyroid swellings. FNAC has excellent patient compliance, is simple and quick to perform in
the outpatient department and is readily repeated. This technique, developed in Scandinavia 40
years ago, is now routine throughout the world. FNAC results should be reported using
standard terminology (Table 50.2). As stated above there is a trend to use ultrasound to guide
the needle to achieve more accurate sampling and reduce the rate of unsatisfactory aspirates.
Optional :
● Corrected serum calcium
● Serum calcitonin (carcinoembryonic antigen may be used as an alternative screening test for
medullary cancer) –
The parafollicular C cells of the thyroid are of neuroendocrine origin and arrive in the
thyroid via the ultimobranchial body. They produce calcitonin.
● Imaging:
1) Ultrasound:
2) Chest radiograph and thoracic inlet view if tracheal deviation/retrosternal goitre.
3) CT and MRI-
4) Positron emission tomography (PET)-

7
 PET scans have limited application in thyroid disease. They may be considered
in the setting of recurrent thyroid cancer. This is particularly useful when the
disease does not concentrate iodine, at which point fluorodeoxyglucose (FDG)
uptake increases and lesions become positive on PET scans.

5) Isotope Scanning-
The uptake by the thyroid of a low dose of either radiolabelled iodine (123I) or
the cheaper technetium (99mTc) will demonstrate the distribution of activity in
the whole gland. Routine isotope scanning is unnecessary and inappropriate for
distinguishing benign from malignant lesions because the majority (80%) of
‘cold’ swellings are benign and some (5%) functioning or ‘warm’ swellings will
be malignant. Its principal value is in the toxic patient with a nodule or
nodularity of the thyroid. Localisation of overactivity in the gland will
differentiate between a toxic nodule with suppression of the remainder of the
gland, and toxic multinodular goitre with several areas of increased uptake with
important implications for therapy.

HYPERTHYROIDISM:
Hyperthyroidism is hyperactivity of the thyroid gland with sustained increase in synthesis and
release of thyroid hormones. Hyperthyroidism occurs in women more than men, with the
highest frequency in persons 20 to 40 years old. The most common form of hyperthyroidism is
Graves’ disease. Other causes include toxic nodular goiter, thyroiditis, excess iodine intake,
pituitary tumors, and thyroid cancer. The term thyrotoxicosis refers to the physiologic effects or
clinical syndrome of hypermetabolism that results from excess circulating levels of T4, T3, or
both. Hyperthyroidism and thyrotoxicosis usually occur together, as seen in Graves’ disease.
The prevalence of hyperthyroidism has been studied in several studies. In an epidemiological
study from Cochin, subclinical and overt hyperthyroidism were present in 1.6% and 1.3% of
subjects participating in a community survey. In a hospital-based study of women from
Pondicherry, subclinical and overt hyperthyroidism were present in 0.6% and 1.2% of subjects.
More than a third of community-detected hyperthyroid cases have positive anti-TPO
antibodies, and about 39% of these subjects have a goiter
Thyrotoxicosis/Thyroid crisrs/ Thyroid Storm:
Thyrotoxicosis is the clinical manifestation of hyperthyroidism. Thyrotoxic crisis, otherwise
known as thyroid storm, is a life threatening condition that involves multi-organ system
dysfunction including severe cardiovascular, thermoregulatory, gastrointestinal, and
neurobehavioral symptoms. It is seen in less than 1% of adults with hyperthyroidism and is
rarer in children. It has a high mortality rate (10-30%) if not recognized early and treated
aggressively.
It is an acute, severe, and rare condition that occurs when excessive amounts of thyroid
hormones are released into the circulation. Although it is considered a life-threatening
emergency, death is rare when treatment is initiated early. Thyrotoxicosis is thought to result
from stressors (e.g., infection, trauma, surgery) in a patient with preexisting hyperthyroidism,
either diagnosed or undiagnosed. Patients particularly prone to thyrotoxicosis are those having

8
a thyroidectomy, since manipulation of the hyperactive thyroid gland results in an increase in
hormones released. In thyrotoxicosis, all the symptoms of hyperthyroidism are prominent and
severe.
Common cause/ Precipitating factors:
Thyrotoxicosis can develop in patients with longstanding untreated hyperthyroidism or it can
be precipitated by an acute event . Thyroid storm is a hypermetabolic and beta-adrenergic
driven state. Over production of thyroid hormones increase the density of beta-adrenergic
receptors enhancing the effect of catecholamines. 90% of thyrotoxicosis is caused by
hyperthyroidism. The most common cause in children is Grave’s Disease. Grave’s disease is an
autoimmune disorder that results in antibody production (TSH receptor stimulating
immunoglobulins) that stimulate TSH receptors resulting in excessive stimulation of the thyroid
gland.
 Primary hyperthyroidism (Grave’s disease, toxic multi-nodular goiter)
 Secondary hyperthyroidism (pituitary adenoma)
 Thyroiditis (postpartum, radiation thyroiditis)
 Drug Induced (lithium, iodine, amiodarone, excessive thyroid hormone ingestion,
anticholinergic drugs, adrenergic drugs)
 Abrupt cessation of anti-thyroid medications
 Thyroid or non-thyroid surgery in a patient with unrecognized hyperthyroidism
 Acute illness (diabetic ketoacidosis, sepsis)
 Trans-placental passage of maternal thyroid stimulating immunoglobulins

CLINICAL MANIFESTATIONS
The diagnosis of thyrotoxic crisis is based upon the presence of severe life threatening
symptoms (cardiovascular dysfunction, altered mental status, hyperpyrexia ) in a patient with
biochemical evidence of hyperthyroidism.

Metabolic: Fever, sweating, metabolic acidosis, hyperventilation, amenorrhea, weight loss

GI System: Nausea, vomiting, diarrhea, abdominal pain, hepatic dysfunction
Cardiac System: Sinus tachycardia out of proportion to the degree of fever, Hypotension,
congestive heart failure, Atrial fibrillation (up to 20% of adults, rare in children), Prolonged QT
interval, High cardiac output produces bounding pulse, widened pulse pressure.
Neuro System: Psychiatric Agitation, delirium, psychosis, stupor, coma Newborns Irritable,
unable to feed appropriately, and have inadequate weight gain, Altered mental status, hand
tremor, hyperreflexia.
Eyes: Staring appearance due to upper eyelid retraction, eyelid lag (both due sympathetic over-
activity). Light sensitivity Grave’s ophthalmopathy (periorbital edema, proptosis) is an
autoimmune mediated inflammation and edema of extraocular muscles and intra-orbital
connective tissue 50-70% of children.
Neck: Smooth, diffusely and symmetrically enlarged goiter. No palpable nodularity. Typically
non-tender to palpation. Bruit over a large vascular gland possible

9
Skin: Warm (cutaneous vasodilation) and moist (diaphoresis) Grave’s dermatopathology
(bilateral non-pitting edema with associated thickening and induration of the skin) Typically
seen over the ankles and feet. Rare in children

10
LABORATORY TESTING: Laboratory findings are consistent with primary hyperthyroidism
 (Low TSH, high free T4/T3). Values are similar to those seen in uncomplicated
hyperthyroidism.
 Abnormal liver function tests (thyroid hormones play a role in the metabolism of
bilirubin)
 Elevated glucose (catecholamine induced inhibition of insulin and increase
glycogenolysis)
 Elevated calcium (increased bone resorption)
 Leukocytosis or leukopenia may be seen.
Collaborative care of Thyroid Crisis:
Initially treatment is directed at inhibiting the peripheral effects of thyroid hormone and
decreasing metabolic rate and cardiac workload.

11
Subsequent treatment is directed at decreasing thyroid hormone production, inhibiting release
and enhancing clearance as well as recognition and treatment of precipitating factors. The
patient should be admitted to an ICU to monitor for clinical deterioration and to provide
ongoing care.
Initial Stabalisation:
 Airway protection, oxygenation, ventilation PRN
 EKG, cardiac monitoring, avoid medications that can prolong the QT interval
 Supportive measures including aggressive cooling e.g. cooling blankets
 Fluid resuscitation (increased insensible fluid losses) A
 cetaminophen for temperature regulation
 Decrease metabolic rate: Beta blockers (e.g. Propranolol)
 Decrease thyroid hormone production: Methimazole, Propylthiouracil Iodine
 Consider corticosteroids, bile acid sequestration (e.g. Cholestyramine)
 Treatment of precipitating factors
 Admit to Intensive Care Unit
 DO NOT GIVE ASPIRIN: Increases T4 by displacing thyroid hormone from protein
binding and increase metabolic demand by uncoupling oxidative phosphorylation
Drug Therapy-
Anti-thyroid drugs: THIONAMIDES
The first-line antithyroid drugs are propylthiouracil (PTU) and methimazole (Tapazole). These
drugs inhibit the synthesis of thyroid hormones.
PROPYLTHIOURACIL (PTU) It decreases synthesis of thyroid hormones within 1-2 hours
Decreases peripheral conversion of T4 to T3
Indications: Preferred for life-threatening illness: Decreases synthesis of thyroid hormones
within 1-2 hours, may more rapidly decrease T3 Preferred during first trimester in pregnancy
due to less teratogenicity compared to Methimazole (can cross the placenta)
Dose: Adolescent/Adult: 500-1000 mg then 250 mg PO Q4 hours
Child: 5-7 mg/day PO divided Q8 hours (maximum 1,200 mg/day)
METHIMAZOLE: It decreases synthesis of thyroid hormones within 1-2 hours
Indications: Preferred for severe illness, Longer duration of action, less hepatotoxic, ultimately
results in euthyroidism faster than PTU Readily crosses placenta and distributes into breast
milk. Safer in children
Dose: Adolescent/Adult: 60-80 mg/day PO/NG divided Q4-6 hours
Infants/Children: 0.5 – 0.7 mg/kg/day PO/NG divided Q8 hours
IODINE:
Iodine is used with other antithyroid drugs to prepare the patient for thyroidectomy or for
treatment of thyrotoxicosis. The administration of iodine in large doses rapidly inhibits
synthesis of T3 and T4 and blocks the release of these hormones into circulation. It also

12
decreases the vascularity of the thyroid gland, making surgery safer and easier. The maximal
effect of iodine is usually seen within 1 to 2 weeks.
Because of a reduction in the therapeutic effect, long-term iodine therapy is not effective in
controlling hyperthyroidism. Iodine is available in the form of saturated solution of potassium
iodine (SSKI) and Lugol’s solution.
Lugol solution: 5% Iodine and 10% Potassium Iodide (126 mg Iodine/ml or 8 mg Iodine per
drop) ,Children/Adolescents: 10 drops PO TID
SSKI (Saturated Solution of Potassium Iodide (38 mg Iodine/drop)
 Infants < 1 year: 150-200 mg PO TID
 Children/Adolescents: 300 to 500 mg PO (5 drops) Q6 hours)
 Adults: 5 drops (0.25 ml or 250 mg) PO Q6 hours
Beta-adrenergic blockers:
β-Adrenergic blockers are used for symptomatic relief of thyrotoxicosis. These drugs block the
effects of sympathetic nervous stimulation, thereby decreasing tachycardia, nervousness,
irritability, and tremors. Propranolol is usually administered with other antithyroid agents.
Atenolol is the preferred β-adrenergic blocker for use in the hyperthyroid patient with asthma
or heart disease.
PROPRANOLOL Inhibits the peripheral effects of thyroid hormone Beta-blocker. Limits B-
adrenergic activity and block peripheral conversion of T4 to T3. Highly lipid soluble, crosses
the blood brain barrier so may help with neurologic symptoms
Indications: Tachycardia, hypertension, agitation
Dose 0.5 – 1 mg IV over 10 minutes then 1-2 mg every few hours
Adolescent/Adult: 60-80 mg PO every 4-6 hours
Infants/Children: 0.5 to 2 mg/kg/day PO divided Q6 hours
Other Drugs:
GLUCOCORTICOIDS :Inhibit thyroid hormone release from the thyroid and decreases
peripheral conversion of T4 to T3 Decrease autoimmune process in Grave’s disease
Indications: Used in extreme cases; patient with CHF, arrhythmias, or shock.
Dose Dexamethasone 0.2 mg/kg (1-2 mg Q6 hours)
Hydrocortisone (adolescent/adult): 300 mg IV, then 100 mg Q8H Hydrocortisone
(infant/child): 1-2 mg/kg Q8 hours
CHOLESTYRAMINE:Thyroid hormones are metabolized in the liver, get secreted into bile
and get reabsorbed if not bound by enterohepatic circulation. Bile acid sequestrants interfere
with enterohepatic circulation and reduce thyroid hormone levels
Dose Adult: 4 grams PO QID

13
Surgical Therapy:
Thyroidectomy is indicated for individuals who have
 a large goiter causing tracheal compression
 been unresponsive to antithyroid therapy,
 thyroid cancer.
A subtotal thyroidectomy is often the preferred surgical procedure and involves the removal
of a significant portion (90%) of the thyroid gland.
An endoscopic thyroidectomy is a minimally invasive procedure. Several small incisions are
made, and a scope is inserted. Instruments are passed through the scope to remove thyroid
tissue or nodules. Endoscopic thyroidectomy is an appropriate procedure for patients with small
nodules (less than 3 cm) and no evidence of malignancy. Advantages of endoscopic
thyroidectomy over open thyroidectomy include less scarring, less pain, and a faster return to
normal activity.
Nutritional Therapy:
A high-calorie diet (4000 to 5000 cal/day) may be ordered to satisfy hunger, prevent tissue
breakdown, and decrease weight loss. This can be accomplished with six full meals a day and
snacks high in protein, carbohydrates, minerals, and vitamins. The protein content should be 1
to 2 g/kg of ideal body weight. Increase carbohydrate intake to compensate for increased
metabolism. Carbohydrates provide energy and decrease the use of body-stored protein. Teach
the patient to avoid highly seasoned and high-fiber foods because these foods can further
stimulate the already hyperactive GI tract. Instruct the patient to avoid caffeine-containing
liquids such as coffee, tea, and cola to decrease the restlessness and sleep disturbances
associated with these fluids. Refer the patient to a dietitian for help in meeting individual
nutritional needs.

Nursing assessment -
 Nursing Diagnoses-
o Nursing diagnoses for the patient with, but are not limited to, the following:
• Activity intolerance related to fatigue and heat intolerance
• Imbalanced nutrition: less than body requirements related to
hypermetabolism and inadequate food intake
 Planning-
o The overall goals are:
 experience relief of symptoms
 have no serious complications related to the disease or treatment
 maintain nutritional balance
 cooperate with the therapeutic plan.
 Nursing Implementation-
Acute intervention-
Acute thyrotoxicosis-

14
  Acute thyrotoxicosis is a systemic syndrome that requires aggressive treatment, often in
an intensive care unit.
 Administer medications that block thyroid hormone production and the sympathetic
nervous system.
 Provide supportive therapy,
 including monitoring for cardiac dysrhythmias and decompensation,
 ensuring adequate oxygenation,
 administering IV fluids to replace fluid and electrolyte losses. This is especially
important in the patient who experiences fluid losses due to vomiting and diarrhea.
 Ensuring adequate rest may be a challenge because of the patient’s irritability and
restlessness. Provide a calm, quiet room because increased metabolism and sensitivity
of the sympathetic nervous system causes sleep disturbances.
 placing the patient in a cool room away from very ill patients and noisy, high-traffic
areas
 using light bed coverings and changing the linen frequently if the patient is diaphoretic.
 encouraging and assisting with exercise involving large muscle groups (tremors can
interfere with small-muscle coordination) to allow the release of nervous tension and
restlessness.
 establish a supportive, trusting relationship to facilitate coping by a patient who is
irritable, restless, and anxious.
 If exophthalmos is present, there is a potential for corneal injury related to irritation and
dryness. The patient may have orbital pain. Nursing interventions to relieve eye
discomfort and prevent corneal ulceration include applying artificial tears to soothe
and moisten conjunctival membranes.
 Salt restriction may help reduce periorbital edema.
 Elevate the patient’s head to promote fluid drainage from the periorbital area. The
patient should sit upright as much as possible.
 Dark glasses reduce glare and prevent irritation from smoke, air currents, dust, and dirt.
 If the eyelids cannot be closed, lightly tape them shut for sleep.
 To maintain flexibility, teach the patient to exercise the intraocular muscles several
times a day by turning the eyes in the complete range of motion.
 Good grooming can help reduce the loss of self-esteem from an altered body image.
For surgical petients:
Preoperative care:
 Before surgery, antithyroid drugs, iodine, and β-adrenergic blockers may be
administered to achieve a euthyroid state. Iodine reduces vascularization of the thyroid
gland, reducing the risk of hemorrhage.
 Iodine is mixed with water or juice, sipped through a straw, and administered after
meals. Assess the patient for signs of iodine toxicity such as swelling of the buccal
mucosa and other mucous membranes, excessive salivation, nausea and vomiting, and
skin reactions. If toxicity occurs, discontinue iodine administration and notify the health
care provider.
 Preoperatively, teach the patient about comfort and safety measures.
 Teach the patient the importance of performing leg exercises.
15
  Instruct the patient on how to support the head manually while turning in bed, since this
maneuver minimizes stress on the suture line after surgery.
 The patient should practice range-of-motion exercises of the neck.
 Explain routine postoperative care such as IV infusions.
 Tell the patient that talking is likely to be difficult for a short time after surgery.
Postoperative care-
 Important nursing interventions after a thyroidectomy include the following:
 Assess the patient every 2 hours for 24 hours for signs of hemorrhage or tracheal
compression such as irregular breathing, neck swelling, frequent swallowing, sensations
of fullness at the incision site, choking, and blood on the anterior or posterior dressings.
 Place the patient in a semi-Fowler’s position and support the patient’s head with
pillows. Avoid flexion of the neck and any tension on the suture lines.13
 Monitor vital signs and calcium levels.
 Complete the initial assessment by checking for signs of tetany secondary to
hypoparathyroidism (e.g., tingling in toes, fingers, around the mouth; muscular
twitching; apprehension) and by evaluating difficulty in speaking and hoarseness.
 Monitor Trousseau’s sign and Chvostek’s sign. Expect some hoarseness for 3 or 4 days
after surgery because of edema.
 Control postoperative pain by giving medication. If postoperative recovery is
uneventful, the patient ambulates within hours after surgery, is permitted to take fluid as
soon as tolerated, and eats a soft diet the day after surgery.
 The appearance of the incision may be distressing to the patient. Reassure the patient
that the scar will fade in color and eventually look like a normal neck wrinkle. A scarf,
jewelry, a high collar, or other covering can effectively camouflage the scar
Ambulatory and home care:
 The patient, caregiver, and family need to be aware that thyroid hormone balance
should be monitored periodically. Most patients experience a period of relative
hypothyroidism soon after surgery because of the substantial reduction in the size of the
thyroid. However, the remaining tissue usually hypertrophies over time and recovers the
capacity to produce hormones. The administration of thyroid hormone is avoided
because the exogenous hormone inhibits pituitary production of TSH and delays or
prevents the restoration of normal gland function and tissue regeneration.
 To prevent weight gain, caloric intake must be reduced substantially below the amount
that was required before surgery. Adequate iodine is necessary to promote thyroid
function, but excesses can inhibit the thyroid gland. Seafood once or twice a week or
normal use of iodized salt should provide sufficient iodine intake. Encourage regular
exercise to stimulate the thyroid gland. Teach the patient to avoid high environmental
temperatures because they inhibit thyroid regeneration.
 Regular follow-up care is necessary. The patient should see the health care provider
sbiweekly for a month and then at least semi-annually to assess thyroid function. If a
complete thyroidectomy has been performed, instruct the patient about the need for
lifelong thyroid hormone replacement. Teach the patient the signs and symptoms of
progressive thyroid failure and to seek medical care if these develop. Hypothyroidism is
relatively easy to manage with oral administration of thyroid replacement.
16
EVALUATION:
The expected outcomes are that the patient with hyperthyroidism will
• Experience relief of symptoms
• Have no serious complications related to the disease or treatment
• Cooperate with the therapeutic plan

HYPOTHYROIDISM
Hypothyroidism is a deficiency of thyroid hormone that causes a general slowing of the
metabolic rate. About 4% of the U.S. population has mild hypothyroidism, with about 0.3%
having more severe disease. Hypothyroidism is more common in women than men.
Studies from Mumbai have suggested that congenital hypothyroidism is common in India, the
disease occurring in 1 out of 2640 neonates when compared with the worldwide average value
of 1 in 3800 subjects.
In childhood too, hypothyroidism can occur. In a clinic-based study from Mumbai, out of 800
children with thyroid disease, 79% had hypothyroidism. Common causes of hypothyroidism in
these children were thyroid dysgenesis, dyshormonogenesis, and thyroiditis.
Among adult people in India, the prevalence of hypothyroidism has been recently studied. In
this population-based study done in Cochin on 971 adult subjects, the prevalence of
hypothyroidism was 3.9%. The prevalence of subclinical hypothyroidism was also high in this
study, the value being 9.4%. In women, the prevalence was higher, at 11.4%, when compared
with men, in whom the prevalence was 6.2%. The prevalence of subclinical hypothyroidism
increased with age. About 53% of subjects with subclinical hypothyroidism were positive for
anti-TPO antibodies.
MYEXEDEMA COMA:
Myxedema coma is a rare fatal condition resulting from long-standing hypothyroidism with
loss of the adaptive mechanism to maintain homeostasis.Myxedema coma represents the most
extreme form of hypothyroidism, so severe as to readily progress to death unless diagnosed
promptly and treated vigorously. The mental sluggishness, drowsiness, and lethargy of
hypothyroidism may progress gradually or suddenly to a notable impairment of consciousness
or coma. This situation, termed myxedema coma, is a medical emergency. Hypothyroidism
due to any cause, including autoimmune disease, iodine deficiency, congenital abnormalities, or
medications like lithium and amiodarone, can precipitate myxedema coma if left untreated.
Even with early diagnosis and treatment of myxedema coma, the mortality rate is variable, with
some reports as high as 60% and others as low as 20 to 25% in the presence of advanced
intensive support care. Early recognition, a thorough history, physical exam, and early
treatment are paramount in managing myxedema coma.
Etiology and Pathophysiology:
Hypothyroidism can be classified as primary or secondary. Primary hypothyroidism is caused
by the destruction of thyroid tissue or defective hormone synthesis. Secondary hypothyroidism
is caused by pituitary disease with decreased TSH secretion or hypothalamic dysfunction with
17
decreased thyrotropin-releasing hormone (TRH) secretion. Hypothyroidism may also be
transient and related to thyroiditis or discontinuance of thyroid hormone therapy.
Iodine deficiency is the most common cause of hypothyroidism worldwide. In the United
States, the most common cause of primary hypothyroidism is atrophy of the thyroid gland. This
atrophy is the end result of Hashimoto’s thyroiditis or Graves’ disease. These autoimmune
diseases destroy the thyroid gland. Hypothyroidism may also develop due to treatment for
hyperthyroidism, specifically the surgical removal of the thyroid gland or RAI therapy. Drugs
such as amiodarone (Cordarone) (contains iodine) and lithium (blocks hormone production)
can cause hypothyroidism.
Hypothyroidism that develops in infancy (cretinism) is caused by thyroid hormone
deficiencies during fetal or early neonatal life. All infants in the United States are screened
for decreased thyroid function at birth.
Myxedema coma: exacerbating or precipitating factors:
 Hypothermia(Extremely cold weather actually seems to lower the threshold for
vulnerability, with an otherwise stable hypothyroid individual slipping into a coma after
cold exposure)
 Cerebrovascular accidents
 Congestive heart failure
 Infections
 Drugs (Anesthetics, Sedatives, Tranquilizers, Narcotics, Amiodarone, Lithium
carbonate) Gastrointestinal bleeding
 Trauma
 Metabolic disturbances exacerbating myxedema coma
 Hypoglycemia
 Hyponatremia
 Acidosis
 Hypercalcemia
 Hypoxemia
 Hypercapnia
 hypothalamic or pituitary disease
Clinical Manifestations:
Cardiac Manifestations
 Diastolic hypertension is one of the cardiovascular compensatory mechanisms in
hypothyroidism.
 Hypothermia and decreased respiratory drive cause peripheral vasoconstriction,
resulting in loss of protective mechanism and development of hypotension.
 shock
 arrhythmia
 Heart block.
 Decreased myocardial contractility and
 Reduced cardiac output, which leads to hypotension.
 Bradycardia

18
  Flattened T waves, low voltage, bundle branch blocks, and complete heart blocks are
common pericardial effusion due to the accumulation of fluid investigation.
 Fatal arrhythmias are important to recognize in Myxedema and chronic
hypothyroidism. QT interval prolongations leading to “torsades de pointes,” which
resolves with treatment of myxedema.
 Myocardial infarction is important to rule out as aggressive T4 replacement may
increase the risk of myocardial infarction.
Neurological Manifestations
 Myxedema coma course is commonly a slow progression to coma.
 Depression,
 Disorientation,
 Decrease deep tendon reflexes,
 Psychosis,
 Slow mentation,
 Paranoia, and
 Poor recall.
 Lumbar punctures, which are usually done during the investigation of underlying
causes to rule out infections, can show increased pressure and high protein count in
these situations, attributable to increased meningeal permeability and cerebral blood
flow and a decrease in metabolism.
Respiratory Manifestations
 Hypoventilation in myxedema coma is due to impaired hypoxic and hypercapnic
ventilatory response and the associated diaphragmatic muscle weakness.The primary
cause of coma in myxedema appears to be due to respiratory depression due to
decreased response to hypercapnia.
 Swelling of the tongue and vocal cords leads to obstructive sleep apnea contributing
to respiratory failure.
 Pleural effusion
 Ascites.
Gastrointestinal Manifestations
 Abdominal pain
 Nausea
 Vomiting
 Ileus(it can lead to megacolon)
 Anorexia
 Constipation
 Ascites.
 Gastrointestinal bleeding
Renal and Electrolyte Manifestations
 Hyponatremia (occurs mainly due to decreased water transport to the distal nephron)
 Decreased glomerular filtration rate.
 Increase in antidiuretic hormone (ADH). patient’s
 Altered mental status and development of a coma( due to hyponatremia).
 Urinary osmolality elevates relative to plasma osmolality.
19
  Bladder atony causing urinary retention.
Hematologic Manifestations
 Risk of bleeding due to an acquired von Willebrand syndrome type 1 and a decrease
in factors V, VII, VIII, IX, and X.
 Hypercoagulable state.
History and physical examination:
Patients most commonly present for emergency services with altered mental status and
hypothermia, below 35.5°C (95.9° F). The lower the body temperature, the worst is the
prognosis. Due to the presence of altered mental status, a definitive history may be difficult to
obtain. Important historical features include any thyroid dysfunction, the dosage of thyroid
medication, adherence with thyroid medication, thyroid surgery, and history of any
drugs that may affect thyroid function. A quick and detailed physical examination is a
must in the initial assessment of myxedema coma. A physical exam can help confirm the
suspicion of thyroid history by findings of no palpable thyroid tissue, goiter, sparse hair, non-
pitting edema, a surgical scar on the neck, or dry skin. Some elderly patients have atypical
presentations, such as decreased mobility.
The salient features in the examination are as follows.
 Altered mentation - can be very subtle, like depressed affect, apathy, decreased
intellectual capacity, confusion, short attention span, and disorientation. Rarely
psychosis and coma. All patients with decreased alertness need to be screened for
depression.
 Hypoventilation and sleep apnea
 Hypothermia - hypoglycemia and cold weather may present as severe hypothermia.
Not every patient is hypothermic, and some patients may be normothermic.
 Dry, cool, and doughy skin (nonpitting edema, puffiness)
 Alopecia
 Decreased mobility
 Delayed reflex relaxation
 Diastolic hypertension followed by hypotension
 Bradycardia
 Bladder dystonia and distention
 Abdominal distention, paralytic ileus causing megacolon
 Fecal impaction (always perform rectal examination)
Evaluation:
A high index of clinician suspicion for myxedema coma is important. As discussed above,
patients who present will most likely be women in the winter months with a history of thyroid
disorders and a precipitating illness. The two most common findings will be altered mental
status and hypothermia, along with common findings of hypothyroidism.

20
Other common signs include hyponatremia, hypotension, bradycardia, and
hypoventilation. Laboratory results in primary hypothyroidism will show severely low or
undetected low serum total T4, free T4, free T3, and elevated TSH. The underlying etiology
for most patients is a primary thyroid failure, but secondary, tertiary, and sick euthyroid
should be in the differential diagnosis
Laboratory Abnormalities in Myxedema Coma
 Anemia (either normocytic or macrocytic anemia) and leukopenia
 Elevated creatinine phosphokinase can lead to misdiagnosis of myocardial infarction
 Elevated transaminases
 Hyperlipidemia due to inhibition of lipoprotein lipase enzyme
 Hypoglycemia due to downregulation of metabolism)
 Hyponatremia with low serum osmolarity and elevated creatinine (increase ADH with
a decreased ability of kidneys to excrete water)
Other Required Investigations
 Septic workup to rule out infection, including cultures and chest X-ray, etc.
 EKG can show bradycardia with non-specific changes, decrease voltage, variable
block, or prolong QT interval
 Arterial blood gases can show hypoxia, hypercapnia, and respiratory acidosis.
 If cardiomegaly is present on imaging studies, further investigations to rule out
pericardial effusion are necessary (echocardiogram)
 Neurological investigations like lumbar puncture usually show elevated protein with
non-specific EEG changes.
Management:
Since myxedema coma has a high mortality rate of up 60%, all patients require admission to
the intensive care unit. There is documented higher mortality in elderly females, cardiac
arrhythmias, persistent hypothermia, reduced consciousness, and sepsis. Treating myxedema
coma is a multisystem challenge. The identification of the precipitating factor is essential.
Respiratory and airway management is a critical component in the management of the
patient.
Frequent monitoring of the arterial blood gas should be performed to monitor the hypercapnia
and hypoxemia. Most will require mechanical ventilation as the altered mental status does
leave patients more prone to aspiration, and airway obstruction could occur due to the
myxedema of the larynx. Patients should not stop receiving ventilator support until the
resolution of both hypercapnia and hypoxemia, as well as the patient regaining
consciousness.
Initiate fluid resuscitation while monitoring sodium and slow rewarming to avoid further
hypotension. Workup for infection etiology, including lumbar puncture, blood, urine cultures,
empiric antibiotics in addition to appropriate imaging and interventions as a working
diagnosis necessitates.

21
Hypothermia should be managed with warming blankets and increasing the temperature in
the room. Care in warming the patient is advised as this will cause peripheral vasodilation
and may lead to hypotension and shock. As the patient receives treatment with thyroid
replacement, the hypothermia will slowly resolve.
If hypoglycemia is present, 5 to 10% dextrose with half normal saline should be
administered carefully. Hypotonic fluids should be avoided.
Low sodium can precipitate altered mental status, and correcting the deficiency is vital. There
is a careful balance between fluid restriction and the need for fluids. A central venous line is
also a recommendation.
If hyponatremia is severe (below 120 mmol/L), careful administration of 3% sodium
chloride along with intravenous bolus furosemide to allow for proper diuresis. A 4 to 6
mmol/L increase in serum sodium concentration is shown to correct many neurological
symptoms. Slow correction is vital as overcorrection increases the risk for osmotic
demyelination syndrome. Current research suggests that the correct rate should not increase
more than 6 to 8 mmol/L in 24 hours.
thyroid hormone therapy Hydrocortisone is recommended to be administered prior to
thyroid hormone therapy, especially if the patient is hypotensive to avoid adrenal crises;
suggestions are that levothyroxine will increase cortisol metabolism, and hypothyroidism
may mask an underlying adrenal insufficiency.A recommended course of therapy, if possible,
is to draw blood for random cortisol, TSH, FT4, FT3 and administer hydrocortisone starting
with a 100 mg IV initiating dose (total 200 to 400 mg daily) which can be stopped or
weaned down based on cortisol when blood levels are back, and hypotension resolves.
Levothyroxine (Synthroid) is the drug of choice to treat hypothyroidism. In the young and
otherwise healthy patient, the maintenance replacement dosage is adjusted according to the
patient’s response and laboratory findings. When thyroid hormone therapy is initiated, the
initial dosages are low to avoid increases in resting heart rate and BP. In the patient with
compromised cardiac status, careful monitoring is needed when starting and adjusting the
dosage because the usual dose may increase myocardial oxygen demand. The increased
oxygen demand may cause angina and cardiac dysrhythmias.recommended initial dose is
200 to 400 mcg IV once (lower dose for elderly, or underlying cardiac disease or arrhythmia
with some reports up to 500 mcg). TSH, FT4, FT3 should be measured at baseline and then
every 24 to 48 hours until the patient's mental status starts to improve
Liotrix is a synthetic mix of levothyroxine (T4) and liothyronine (T3) in a 4:1 combination.
Levothyroxine has a peak of action of 1 to 3 weeks. In contrast, liotrix has a faster onset of
action with a peak of 2 to 3 days. Liotrix can be used in acutely ill individuals with
hypothyroidism.
Nursing management;
Nursing Assessment:
 Careful assessment may reveal early and subtle changes in a patient
suspected of having hypothyroidism. Note any previous history of
hyperthyroidism and treatment with antithyroid medications, radioactive
iodine, or surgery. Ask the patient about prescribed iodine-containing
medications and any changes in appetite, weight, activity level, speech,
memory, and skin such as increased dryness or thickening. Assess for

22
 cold intolerance, constipation, and signs of depression. Further
assessment should focus on heart rate, tenderness over the thyroid gland,
and edema in the extremities and face.
o Nursing Diagnoses:
 Nursing diagnoses may include, but are not limited to, the following:
- Imbalanced nutrition: more than body requirements related to
calorie intake in excess of metabolic rate
- Constipation related to GI hypomotility
- Impaired memory related to hypometabolism
o Planning:
 The overall goals are that the patient with hypothyroidism will
- experience relief of symptoms
- maintain a euthyroid state
- maintain a positive self-image
- comply with lifelong thyroid therapy.
o Nursing Implementation:
 Health Promotion:
- Currently no consensus exists regarding thyroid function
screening. Although hypothyroidism is relatively common,
particularly among women over age 50, there does not appear to
be strong justification for screening the general population. High-
risk populations should be screened for subclinical
(asymptomatic) thyroid disease. High-risk individuals include
those with a family history of thyroid disease, those with a
history of neck radiation, women over 50 years old, and
postpartum women.
 Acute Intervention:
The patient who develops a myxedema coma requires acute
nursing care, often in an intensive care setting. Mechanical
respiratory support and cardiac monitoring are frequently
necessary.
- Administer thyroid hormone therapy and all other medications
IV because paralytic ileus may be present in myxedema coma.
Monitor the core temperature because hypothermia often
occurs in myxedema coma. Use soap gently and moisturize
frequently to prevent skin breakdown. Frequent changes in
patient positioning and a low-pressure mattress can also assist in
maintaining skin integrity. Monitor the patient’s progress by
assessing vital signs, body weight, fluid intake and output, and
visible edema. Cardiac assessment is especially important
because the cardiovascular response to hormone therapy
determines the medication regimen. Note energy level and mental
alertness, which should increase within 2 to 14 days and continue
to improve steadily to normal levels. The patient’s neurologic
status and free T4 levels are used to determine continuing
treatment

23
  Ambulatory and Home care:
- Patient teaching is essential for the patient with hypothyroidism
and the caregiver. Initially the hypothyroid patient may have
difficulty processing complex instructions. It is important to
provide written instructions, repeat the information often, and
assess the patient’s comprehension level.
- Stress the need for receiving lifelong drug therapy and avoiding
abrupt discontinuation of drugs. Instruct the patient in expected
and unexpected side effects. In the teaching plan include the signs
and symptoms of hypothyroidism or hyperthyroidism that
indicate hormone imbalance. Clearly define toxic symptoms.
- Teach the patient to immediately contact a health care provider if
manifestations of overdose occur, such as orthopnea, dyspnea,
rapid pulse, palpitations, chest pain, nervousness, or insomnia.
The patient with diabetes mellitus should test his or her capillary
blood glucose at least daily because the return to the euthyroid
state frequently increases insulin requirements. In addition,
thyroid drugs potentiate the effects of anticoagulants and
decrease the effect of digitalis compounds. Instruct the patient
about the toxic signs and symptoms of these medications and the
need to remain under close medical observation until stable.
- With treatment, striking transformations occur in both appearance
and mental function. Most adults return to a normal state.
Cardiovascular conditions and (occasionally) psychosis may
persist despite corrections of the hormonal imbalance. Relapses
occur if treatment is interrupted.
o Evaluation:
 The expected outcomes are that the patient with hypothyroidism will
o Have relief from symptoms
o Maintain a euthyroid state as evidenced by normal thyroid
hormone and TSH levels
o Avoid complications of therapy
o Adhere to lifelong therapy

Adrenal gland:

24
Adrenal glands are endocrine glands located on top of your kidneys. They produce many
important hormones, including cortisol, aldosterone and adrenaline. The adrenal hormones help
regulate several bodily functions including metabolism, blood pressure and body's response to
stress.

An adrenal gland is made of two main parts:

 The adrenal cortex is the outer region and also the largest part of an adrenal gland. It
is divided into three separate zones: zona glomerulosa, zona fasciculata and zona
reticularis. Each zone is responsible for producing specific hormones.
 The adrenal medulla is located inside the adrenal cortex in the center of an adrenal
gland. It produces “stress hormones,” including adrenaline.
The adrenal cortex and adrenal medulla are enveloped in an adipose capsule that forms a
protective layer around an adrenal gland.

Hormones of the Adrenal Glands

The role of the adrenal glands is to release certain hormones directly into the bloodstream.
Many of these hormones have to do with how the body responds to stress, and some are vital
to existence. Both parts of the adrenal glands ,the adrenal cortex and the adrenal medulla
perform distinct and separate functions.

Each zone of the adrenal cortex secretes a specific hormone. The key hormones produced by
the adrenal cortex include:
Cortisol;

Cortisol is a glucocorticoid hormone produced by the zona fasciculata that plays several
important roles in the body. It helps control the body’s use of fats, proteins and
carbohydrates; suppresses inflammation; regulates blood pressure; increases blood sugar; and
can also decrease bone formation.

This hormone also controls the sleep/wake cycle. It is released during times of stress to help
your body get an energy boost and better handle an emergency situation.

25
How Adrenal Glands Work to Produce Cortisol

Adrenal glands produce hormones in response to signals from the pituitary gland in the brain,
which reacts to signaling from the hypothalamus, also located in the brain. This is referred to
as the hypothalamic pituitary adrenal axis. As an example, for the adrenal gland to produce
cortisol, the following occurs:

 The hypothalamus produces corticotropin-releasing hormone (CRH) that stimulates

the pituitary gland to secrete adrenocorticotropin hormone (ACTH).
 ACTH then stimulates the adrenal glands to make and release cortisol hormones into
the blood.
 Normally, both the hypothalamus and the pituitary gland can sense whether the blood
has the appropriate amount of cortisol circulating. If there is too much or too little
cortisol, these glands respectively change the amount of CRH and ACTH that gets
released. This is referred to as a negative feedback loop.
 Excess cortisol production can occur from nodules in the adrenal gland or excess
production of ACTH from a tumor in the pituitary gland or other source.

Aldosterone

This mineralocorticoid hormone produced by the zona glomerulosa plays a central role in
regulating blood pressure and certain electrolytes (sodium and potassium). Aldosterone sends
signals to the kidneys, resulting in the kidneys absorbing more sodium into the bloodstream
and releasing potassium into the urine. This means that aldosterone also helps regulate the
blood pH by controlling the levels of electrolytes in the blood.

DHEA and androgenic steroids:

These hormones produced by the zona reticularis are weak male hormones. They are
precursor hormones that are converted in the ovaries into female hormones (estrogens) and in
the testes into male hormones (androgens). However, estrogens and androgens are produced
in much larger amounts by the ovaries and testes.

Epinephrine and norepinephrine:

The adrenal medulla, the inner part of an adrenal gland, controls hormones that initiate the
flight or fight response. The main hormones secreted by the adrenal medulla include
epinephrine (adrenaline) and norepinephrine (noradrenaline), which have similar functions.

Among other things, these hormones are capable of increasing the heart rate and force of
heart contractions, increasing blood flow to the muscles and brain, relaxing airway smooth
muscles, and assisting in glucose (sugar) metabolism. They also control the squeezing of the
blood vessels (vasoconstriction), helping maintain blood pressure and increasing it in
response to stress.

Like several other hormones produced by the adrenal glands, epinephrine and norepinephrine
are often activated in physically and emotionally stressful situations when your body needs
additional resources and energy to endure unusual strain.

ADRENAL CRISIS:

26
Adrenal crisis, or Addisonian crisis, is a severe, life-threatening condition characterized by
acute adrenal insufficiency. This condition has a substantial mortality rate of 0.5 per 100
patient-years and remains a significant cause of death in individuals with adrenal
insufficiency. Patients can experience rapid deterioration without timely intervention,
potentially resulting in fatal outcomes either at home or shortly after hospital admission.
This endocrine emergency arises when the production of cortisol, the primary glucocorticoid
(GC) adrenal hormone, is inadequate either due to internal or external factors. Early
recognition and immediate intervention are crucial for saving a patient's life and improving
survival rates
Adrenal crisis is defined by an acute deterioration in health status that is associated with the
following conditions:
 Absolute hypotension with a systolic blood pressure <100 mm Hg.
 Relative hypotension with a systolic blood pressure ≥20 mm Hg lower than the
patient's usual baseline.
History of Adrenal Crisis
In 1855, Thomas Addison's pioneering work provided the earliest description of adrenal
insufficiency, marking a significant milestone in comprehending this condition.[6] The
discovery of cortisone by Hench, Kendall, and Reichstein in the late 1940s revolutionized the
treatment of adrenal insufficiency, leading to a remarkable enhancement in the life
expectancy of individuals affected by this condition.
In the 1930s, tuberculosis was the most prevalent cause of this condition, accounting for
approximately 70% of cases. In recent times, autoimmune adrenalitis, or Addison's disease,
has emerged as the leading cause of primary adrenal insufficiency in developed countries. In
contrast, tuberculosis remains the leading cause of adrenal insufficiency in developing
countries.
Precipitating Factors for Adrenal Crisis
Acute adrenal crisis can be the initial presentation of undiagnosed adrenal insufficiency,
potentially occurring in up to 50% of patients who have already been diagnosed with this
condition. The primary causes of adrenal crises are as follows:
 Bacterial, mycobacterial, fungal, parasitic, or viral, such as COVID-19, infections
 Gastrointestinal and flu-like illnesses
 Trauma, pregnancy, childbirth, surgery, exposure to extreme hot or cold weather, or
other stressful situations
 Significant emotional distress
 Strenuous physical activity
 Nonadherence to GC replacement therapy
 Abrupt cessation of chronic GC therapy
 Thyrotoxicosis, as it accelerates cortisol metabolism.
 Levothyroxine therapy initiation in a previously untreated case of adrenal
insufficiency
27
  Antiadrenal medications, including mitotane, metyrapone, ketoconazole
 Anticancer medications, including immunotherapy with checkpoint inhibitors and
tyrosine kinase inhibitors.
Epidemiology:
Patients with adrenal insufficiency have been estimated to experience an adrenal crisis in 6%
to 8% of cases annually. The incidence of adrenal crises remains high even among patients
who have received extensive education.The annual frequency of adrenal crisis in patients
with Addison's disease remains at 8%.
Risk Factors for Adrenal Crisis
The risk factors associated with adrenal crisis are as follows:
 A known history of adrenal insufficiency or previous adrenal crisis
 Primary adrenal insufficiency diagnosis, which carries a higher risk than secondary
adrenal insufficiency
 Ongoing GC therapy, including topical and inhalation forms, which poses a risk for an
adrenal crisis due to the potential suppression of the hypothalamic-pituitary-adrenal
(HPA) axis, if abruptly discontinued
 Medications, including levothyroxine, phenytoin, phenobarbital, rifampin,
carbamazepine, St John's wort, ketoconazole, etomidate, and fluconazole,
which affect cortisol metabolism or reduce its production
 Anticoagulation agents, which increase the risk of adrenal hemorrhage
 Pregnancy, particularly during the third trimester
 Advanced age
 The presence of comorbidities
 Patients with type 1 diabetes
 Adrenal metastasis or adrenal hemorrhage
Pathophysiology:
Cardiovascular System
GCs have a permissive effect on the functioning of adrenergic receptors in the heart and
vasculature. Without GCs, catecholamines cannot exert their full impact on these receptors.
Consequently, during an adrenal crisis, patients often experience hypotension, and in severe
cases, they may develop profound shock that remains unresponsive to fluid resuscitation and
vasopressor therapy.
Immune System
Infectious or noninfectious stressors can trigger the activation of the immune system, leading
to an elevated release of cytokines. Interleukin (IL)-1, IL-2, IL-6, tumor necrosis factor
(TNF)-α, and TNF-γ have pivotal roles in this immune response. This immune activation
subsequently leads to the activation of the HPA axis, resulting in elevated GC levels.

28
GCs mitigate immune response by inhibiting cytokine production, release, and effects,
thereby playing a crucial role in immune regulation. During an adrenal crisis, any significant
stressor can trigger an uncontrolled cytokine response, such as inflammation, resulting in
fever, widespread vasodilation, and heightened capillary permeability. This can result
in hypovolemia and shock as a consequence of fluid shifting from capillaries into tissues,
thereby contributing to the development of hypovolemic shock.
To sum up, during an adrenal crisis, the dysregulation of the immune response, marked by an
excessive cytokine release, can result in systemic inflammation, fever, vasodilation,
capillary leakage, hypovolemia, and shock.
Intravascular Volume
GCs can potentially suppress the expression and secretion of antidiuretic hormone (ADH) in
the hypothalamic neurons. During an adrenal crisis, there is an upsurge in the activity of
ADH, leading to increased diuresis and volume depletion.
Glucose Homeostasis
GCs increase glucose levels in response to stress through various mechanisms, including
promoting glycogenolysis and stimulating gluconeogenesis. In addition, GCs also induce
insulin resistance, which reduces glucose uptake by the peripheral cells. During an adrenal
crisis, the deficiency of GCs hinders these normal stress responses. As a result of the GC-
deficient state, hypoglycemia can occur due to insufficient glucose production and improved
peripheral utilization.
Appetite Regulation
Corticotropin-releasing hormone (CRH) is a potent appetite suppressant in response to stress.
GCs are potent inhibitors of CRH release that can lead to increased appetite. During an
adrenal crisis, the release of CRH remains uninhibited in the GC-deficient state and leads to
anorexia.
Electrolyte Disturbances
Primary adrenal insufficiency causes mineralocorticoid deficiency due to direct destruction of
the adrenal cortex. However, the cortex remains intact in secondary and tertiary adrenal
insufficiency. The renin-angiotensin-aldosterone system regulates aldosterone production and
secretion. An isolated deficiency of adrenocorticotropic hormone (ACTH) secretion observed
in secondary or tertiary adrenal insufficiency does not significantly affect aldosterone
levels. In primary adrenal insufficiency, aldosterone deficiency leads to volume loss,
hyponatremia, and hyperkalemia.
Clinical menifestation:
 weakness, severe fatigue
 unintentional weight loss
 nausea, vomiting
 abdominal pain
 reduced appetite
 back or limb pain
 dizziness
 somnolence
 confusion, and loss of consciousness.
 Fever
29
  Tachycardia
 orthostatic hypotension.
 Hypoglycemia
Diagnostic evaluation:
In the context of an adrenal crisis, there may be several laboratory abnormalities. However,
the classic laboratory features that may be revealed include:
 Hyponatremia, resulting from mineralocorticoid deficiency
 Hyperkalemia, resulting from mineralocorticoid deficiency
 Hypoglycemia, stemming from decreased gluconeogenesis and glycogenolysis
 Low or low normal ACTH levels, as observed in secondary adrenal insufficiency
 High or high normal ACTH levels, as observed in primary adrenal insufficiency
 Hypercalcemia, resulting from hypovolemia
 Elevated creatinine levels, attributed to prerenal failure
 Low aldosterone levels, due to mineralocorticoid deficiency in primary adrenal
insufficiency
 High renin levels, as typically seen in primary adrenal insufficiency due to increased
urinary sodium loss and reduced blood volume
 Normocytic normochromic anemia, lymphocytosis, and eosinophilia, resulting from
GC deficiency
 Increased thyroid-stimulating hormone (TSH) levels, owing to coexisting
hypothyroidism in autoimmune polyglandular endocrinopathy or the absence of
cortisol's inhibitory effect on TSH production
Evaluation of Cortisol Levels
 ACTH: High ACTH levels with low cortisol and aldosterone indicate primary adrenal
insufficiency, whereas low ACTH levels with low cortisol suggest secondary or
tertiary adrenal insufficiency.
 Basic metabolic panel: A basic metabolic profile blood test, including glucose, should
also be included in the recommended blood work.
 Other blood tests: Additional blood work includes determining cortisol, aldosterone,
and renin levels.
Management:

Emergent management:
1. Establish intravenous access with a large-gauge needle.
2. Draw blood for immediate serum creatinine, BUN, electrolytes, glucose, and routine
measurement of plasma cortisol and ACTH. Do not wait for laboratory results.
3. Infuse 1 liter of isotonic saline or 5% dextrose in isotonic saline as quickly as possible.
Repeat fluid bolus as needed for volume resuscitation, followed by maintenance fluids.
30
 Frequent hemodynamic monitoring and measurement of serum electrolytes should be
performed to avoid iatrogenic fluid overload.
4. Give hydrocortisone (100 mg intravenous bolus), followed by 50 mg intravenously every 6
hours (or 200 mg/24 hours as a continuous intravenous infusion for the first 24 hours). If
hydrocortisone is unavailable, alternatives include methylprednisolone and dexamethasone.
Saline must be administered if dexamethasone is given instead of hydrocortisone.

Subacute measures after stabalization of patients:

1. Use supportive measures as needed. Continue intravenous isotonic saline at a slower rate for
next 24 to 48 hours.
2. Search for and treat possible infectious precipitating causes of the adrenal crisis.
3. Taper parenteral glucocorticoid over 1 to 3 days, if precipitating or complicating illness
permits, to oral glucocorticoid maintenance dose.
4. For patients with primary adrenal insufficiency, begin mineralocorticoid replacement with
fludrocortisone, 0.1 mg by mouth daily, when saline infusion is stopped or hydrocortisone
dose is tapered to <40 mg daily.
5. If the patient does not have known adrenal insufficiency, confirm the diagnosis and determine
the underlying cause.

31
REFERENCES

1. Penman ID, Ralston SH, Strachan MWJ, Hobson R, editors. Davidson’s principles and
practice of medicine. 24th ed. London, England: Elsevier Health Sciences; 2022.
2. Brown D, Edwards H. Lewis’s medical-surgical nursing: Assessment and management
of clinical problems. 3rd ed. Chatswood, NSW, Australia: Mosby; 2011.
3. Fauci AS. Harrison’s principles of internal medicine: Editors, Anthony S. fauci ... [ET
Al.]. 17th ed. Maidenhead, England: McGraw-Hill Education; 2008.
4. Williams N, O’Connell PR, McCaskie A, editors. Bailey & love’s short practice of
surgery, 27th edition: The collector’s edition. 27th ed. New York, NY: Productivity
Press; 2018.
5. Unnikrishnan AG, Menon UV. Thyroid disorders in India: An epidemiological
perspective. Indian J Endocrinol Metab [Internet]. 2011;15(Suppl 2):S78-81. Available
from: http://dx.doi.org/10.4103/2230-8210.83329
6. Ellis H. The clinical examination of the thyroid gland. Br J Hosp Med (Lond) [Internet].
32
2007;68(Sup9):M154–5. Available from:
http://dx.doi.org/10.12968/hmed.2007.68.sup9.27183

33