Endocrinology lecture 5

ADRENAL INSUFFICIENCY

Manal Kh. Abdulrazak

Professor of Internal Medicine
Department of Medicine
College of Medicine - University of Baghdad
 Objectives
By the end of this lecture, the student will be able to:
 Define adrenal insufficiency.
 List the causes of adrenal insufficiency.
 Describe clinical presentation of Addison’s disease.
 Outline the plan of management of Addison’s
disease.
 Define adrenal crisis and recognize its clinical
features.
 Identify the lines of treatment of adrenal crisis.
 CASE SCENARIO 1
❑ A 35-year old female is admitted to the ICU with fever,
chills, dysuria, diarrhea, marked dizziness, anorexia,
nausea, vomiting and abdominal pain for 4 days. On
examination:
❑ She is ill-appearing
❖ Temperature= 39C, PR= 98/minute
❖ BP= 100/70 mm/Hg/ supine position
❖ BP= 80/56 mm/Hg/ standing
❖ Abdominal exam shows mild diffuse tenderness.
❖ BUN= 25 mg/dl (n= 7-22), Cr.= 1.2mg/dl (n= 0.7-1.5)
❖ FBS= 60 mg/dl (n= 70-110)
She had a brain tumor removed 2 years ago and has
been on multiple hormone replacement medicines
since then, none of which have been taken for the past
3 days because of nausea.
 ADRENAL INSUFFICIENCY (AI)
Definition:
 There is a decrease in the secretion of cortisol and or
aldosterone.
 Variable presentation and potentially fatal.
 Prevalence of permanent adrenal insufficiency is 5 in 10,000.
CAUSES
Secondary (low ACTH) is the most common.
 Pituitary tumors (endocrine adenomas, rarely carcinoma).
 Mass lesions affecting the HP region (craniopharyngioma,
meningioma, metastases).
 Pituitary irradiation.
 Pituitary apoplexy/hemorrhage.
 Pituitary infiltration (TB, actinomycosis, sarcoidosis, Wegener's
granulomatosis, metastases).
 Chronic glucocorticoid excess.
 Combined pituitary hormone deficiency (CPHD).
 Congenital isolated ACTH deficiency.
Primary (high ACTH) Addison’s disease:
 Autoimmune (sporadic or polyglandular failure, APS1 and
APS2).
 Adrenal infection (TB, HIV, CMV, cryptococcosis,
histoplasmosis, coccidioidomycosis).
 Adrenal infiltration (Metastases, lymphomas, sarcoidosis,
amyloidosis, hemochromatosis).
 Bilateral adrenalectomy.
 Adrenoleukodystrophy (ALD).
 Adrenal hemorrhage (Meningococcal sepsis)
antiphospholipid syndrome.
Imparied Steriodiogensis
 CAH, Drugs (ketoconazole, etomidate, metyrapone etc)
 Epidemiology
 Addison’s disease is a rare and chronic disease.
 Prevalence of 2 in 10,000 per year.
 Usually effects 30-50 year-olds, but can be seen in all
ages.
 AI arising from suppression of the HPA axis as a
consequence of exogenous glucocorticoid treatment
occurs in 0.5–2% of the population in developed
countries.
 Clinical Features
 Signs and Symptoms Caused by
Glucocorticoid Deficiency:
 Chronic fatigue
 Weight loss, anorexia
 Myalgia, joint pain
 Hypoglycemia, Hyponatremia due to loss of feedback
inhibition of ADH release
 Anemia, eosinophilia and lymphocytosis
 Low blood pressure, postural hypotension
 Fever
 Slightly increased TSH (due to loss of feedback
inhibition of TSH release)
Signs and Symptoms Caused by
Mineralocorticoid Deficiency (Primary AI Only) :

❑Abdominal pain, nausea, vomiting

❑Dizziness, postural hypotension
❑Salt craving
❑Low BP, postural hypotension
❑Increased serum creatinine (due to volume
depletion)
❑ Hyponatremia
❑Hyperkalemia
 Signs and Symptoms Caused by
Adrenal Androgen Deficiency:
 Lack of energy
 Dry and itchy skin (in women)
 Loss of libido (in women)
 Loss of axillary and pubic hair (in women)
Other Signs and Symptoms:
 Hyperpigmentation (primary AI only) [due to excess
of pro-opiomelanocortin (POMC)–derived peptides]
 Alabaster-colored pale skin (secondary AI only)
(due to deficiency of POMC- derived peptides)
 ACUTE ADRENAL INSUFFICIENCY

❑More frequently observed in patients with

primary AI.
❑Postural hypotension may progress to
hypovolemic shock.
❑ AI may mimic features of acute abdomen.
❑May resemble neurologic disease, with
decreased responsiveness, progressing to
stupor and coma.
❑An adrenal crisis can be triggered by an
intercurrent illness, surgical stress, infection.
 DIAGNOSIS
 Determined by low level of adrenal hormone after
stimulation with synthetic ACTH hormone
(tetracosactide or short Synacthen test)
Short Test:
❑ 250 µg of cosyntropin i.m or i.v injection
❑ Blood cortisol levels 30- 60 min
(cortisol post cosyntropin is < 500 nmol/l)
❑ CBC, serum Na, K, creatinine, urea, TSH
For dDx:
Plasma ACTH, renin, S. aldosterone.
❑High ACTH, high PRA, low aldosterone (primary AI)
❑Low- normal ACTH, normal PRA and aldosterone
(secondary)
❑ Adrenal autoantibody
❑ Antibodies against (steroid secreting cells,
thyroid Ag, parietal cells, pancreatic cells)
❑ CBC to look for pernicious anemia
❑ Blood Ca and glucose
❑ CXR, U/S and X-ray of adrenals for TB
calcifications
❑ CT or MRI of adrenals for malignancies,
hemorrhage.
❑ HIV test
❑ Serum Na and K
❑ Tests for 17OHP and in men plasma VLCFA.
❑ MRI pituitary for hypothalamic pituitary mass.
 TREATMENT
❑ Replacement (always need glucocorticoid and
usually mineralcorticoid therapy).
❑ Cortisol orally 15 mg at morning and 5 mg at
evening
(1 mg hydrocortisone, 1.6 mg cortisone acetate, 0.2
mg prednisolone, 0.25 mg prednisone, and 0.025
mg dexamethasone).
❑ Doses change according to lifestyle, i.e. stress,
infection, or injury
❑ Have to carry emergency injection of
hydrocortisone and steroid card/bracelet
indentifying their condition.
❑ Monitor treatment by body w.t and BP.
❑ Mineralocorticoid replacement is by giving
fludrocortison 0.05- 0.1 mg/day
❑ Adrenal androgen replacement is an option in
patients with lack of energy, despite optimized
glucocorticoid and mineralocorticoid
replacement.
❑ It may also be indicated in women with loss of
libido.
❑ Replacement can be achieved by once-daily
administration of 25–50 mg DHEA. Treatment
is monitored by measurement of DHEAS,
androstenedione, and testosterone.
 CASE SCENARIO 2
A 32-year-old woman with known hypothyroidism is
admitted to hospital. Her BP is 86/53 mmHg and
her pulse 100 bpm. Investigations reveal:

Serum Na: 126 mmol/L (137-144)

Serum K: 5.8 mmol/L (3.5-4.9)
Serum glucose: 3.0 mmol/L (3.0-6.0)

❑What is the most likely diagnosis?

❑What is the most appropriate investigation to
confirm your diagnosis?
 ADDISONIAN CRISIS

❑Severe hypotension (shock)

❑Hyperkalemia
❑Hyponatremia
❑Hypoglycemia
❑Unexplained fever, diarrhea, vomiting
❑Could cause coma and death
❑Precipitated by infection, surgery or
intercurrent disease
 TREATMENT
❑ It is a medical emergency.
❑ IV fluid( normal saline 1L/h and 10% dextrose
followed by 4-6 L over 24h).
❑ Hydrocortisone 100 mg bolus then 100- 200 mg
over 24h (infusion or multiple injections) until GI
symptoms improve then start oral therapy.
❑ Mineralocorticoid replacement can be initiated
once the daily hydrocortisone dose has been
reduced to <50 mg.
❑ Treat precipitated cause.
 SUMMARY
 Addison's disease occurs in all age groups and
affects both sexes.
 Addison's disease can be life-threatening.
 Addison's disease symptoms usually develop
slowly, often over several months, sometimes, the
signs and symptoms of Addison's disease may
appear suddenly (addisonian crisis)

 FURTHER READINGS
Davidson’s Principles of Internal Medicine 20th
Edition.
Harrison’s Principles of Internal Medicine 18th
Edition.