Adrenocortical hypofunction Flashcards
What are the categories/causes of adrenocortical hypofunction?
1) Primary defects of the entire gland
Addison’s disease = primary adrenal insufficiency
- Autoimmune, sporadic, 70% of all cases. medulla is in tact.
- Autoimmune Polyendocrine syndromes type 1 and 2
- Infections,
- tuberculosis, fungal, virus,
- waterhouse friedrichsen syndrome
- Infiltrations
- Hemochromatosis
- Amyloidosis
- Metastatic tumors
- ACTH resistance syndromes
2) Secondary due to inadequate ACTH
3) Specific enzyme deficits
- CAH, defective aldosterone and cortisol, excessive androgens.
- 21-OHase deficiency 90%
- 11-OHase deficiency ~5%
- 11 deosycortisol accumulates, a mineralocorticoid agonist.
What is the most common cause of addisons disease?
What are some of its characteristics?
Autoimmune adrenalitis. Since it is autoimmune, Women are more prevalent. Medulla is in tact. Autoantibodies are present
50% have other associated autoimmune disorders - and present as part of Autoimmune Polyendrocrine Syndrome 1 or 2
APS1, APS2
Both involve of AIRE mutations, AutoImmune REgulator gene. -thymic epithelial cells, involved in tissue antigen presentation and self tolerance.
APS1: Adrenalitis, HypoParathyroidism, Pernicious anemia (parietal cells), HypoGonadism.
APS1 = APECED, autoimmune polyendocrinopathy, candidiasis, and ecodermal dystrophy.
APS2: Adrenalitis, Thyroiditis, T1DM.
note: not all of the patients have more than one of the endocrine disorders, lots only have 1, also, many of them have other non-endocrine autoimmune diseases
What are the common infections causing adrenal hypofunction?
What patients are they seen in?
Tuberculosis,
Cryptococcus and histoplasmosis, CMV, all in AIDS patients.
What are the metastatic tumors that can cause adrenal insufficiency?
Breat, Lung, although metastsis to the adrenals is rare.
When can adrenal gland necrosis/atrophy cause adrenal insufficiency?
Waterhouse friedrichsen synd
- Neisseria
- Renal vein thrombosis
- Hypercoagulable states
- Primary antiphospholipid syndrome
Any severely sick patient, with sever trauma, infection or coagulopathy.
- Even in individuals with previously intact HPA axi s
- Functional adrenal insufficiency
- Hypoadrenia is transient, no structural lesion
- Uncertain etiology
- Inability to mount an adequate and appropriate cortisol response to stress on intensive care units
- Increases the risk of death during acute illness
- Treatment with relatively high doses of hydrocortizon, or with methylprednisolon in septic shock, and early phase of acute respiratory distress is recommended
Secondary causes of adrenal insufficiency
- Glucocorticoid therapy
- Hypopituitarism
- Selective removal of ACTH secreting pit. adenoma
- Pituitary tumors, and pituitary surgery, craniopharyngeomas, pituitary apoplexy, pituitary irradiation
- Granulomatous disease
- Postpartum pituitary infarction (Sheehan’s sy)
- Secondary tumor deposits
- Isolated ACTH deficiency, Multiple pituitary hormon deficiencies
What are the congenital causes of primary adrenal insufficiency?
Congenital Adrenal Hypoplasia - X linked disorder, with combined hypogonadism.
Adrenoleukodystrophy - X linked disorder disease of very-long chain fatty acid metabolism, due to ABCD1 transporter protein. Progressive neurological demyelination, and adrenal insufficiency developing in childhood.
Familial glucocorticoid deficiency - Inherited defect in the ACTH receptor.
Triple A syndrome - rare disease, addisons, achalasia (constant smooth muscle contraction), and alacrima.
What are the symptoms of primary adrenal insufficiency?
- Weakness, tiredness, fatigue - gradually 99%
- Pigmentation of skin 98%
- Anorexia, weight loss 97%
- Gastrointestinal symptoms: nausea, vomiting,(90%) constipation, abdominal pain (34%), diarrhoea (20%) – it can cause Addison’s crisis - “think of addisons in patients with unexplained abdominal symptoms”
-
Hypotension
- Decreased Kidney perfusion
- Decreased GFR
- Azotemia
- Anemia
- Acidosis
- Hyponatermia - decreased aldosterone and salt wasting
- Hyperkalemia
- Hypercalcemia -“unclear reasons”
- Salt craving – muscle spasm (22%)
- Postural dizziness, syncope (16%)
- Vitiligo (9%)
Characteristics of an Addisonian crisis
Medical emergency
Dehydration, hypotension or shock out of proportion to severity of current illness
Nausea and vomiting, with a history of anorexia
Acute abdomen
Unexplained hypoglycaemia
Unexplained fever
Tests for adrenal function
plasma corisol, and urinary cortisol
basal cortisol should be above 14.5 ug/dL
Synacthen Iv stimulation and cortisol/ldosterone measurement 18g/dl and 5ng/dl should be reached in 30 mins.
What is the treatment for acute adrenal insufficiency?
If suspected, treatment should not be delayed for definitive proof.
“Unexplained hyponatremia and hyperkalemia in the setting of hypotension unresponsive for catecholamin and fluid administration…..should receive 100 mg hyrocortisone intravenously”
Essentially: Replace fluid and sodium to prevent hypovolemia and hyponatremia, and replace cortisol.
Plasma electrolyte, glucose and appropriate samples for ACTH and cortisol should be taken before CS therapy
Then: 2-3 L of 0.9% NaCl solution, or 50 g/l (5%) dextrose in 0.9% saline solution as soon as possible
Monitor fluid overload by measuring central venous pressure
Iv 100 mg hydrocortison and every 6 hr
What is the long term treatment for chronic adrenal insufficiency
Glucocorticoid and Mineralocorticoid replacement, every day.
DHEA supplementation is controversial: Can improve mood/well being, is recommended for postmenopausal women.
Cortisol replacement:
- Cortisol taken with meals, 2/3 dose in the morning 1/3 dose in afternoon - mimic the diurnal rythm.
- During infections and fevers: double the cortisol dose
- During severe illness, the dose is increased by 3-5 times.
- Especially during surgery
Aldosterone replacement:
- Fludrocortisone (aldosterone agonist)
- Take increased dose and consume extra salt whenever they dos omething that causes sweating, diarrhea, or extremely hot weather.
Requires thorough patient education about the disorder and medication.
Main cause of secondary adrenal insufficiency?
Iatrogenic, excessive exogenous glucocorticoids, and subsequent withdrawal.
Atrophy of the pituitary corticortropic cells causes low ATCH levels. Reversible, but can take up to a year. Only cortisol is affected, and the aldosterone levels are maintained by Angiotensin.
What are the main symptoms and presentation of APS1?
APS1: Adrenalitis, HypoParathyroidism, Pernicious anemia (parietal cells), HypoGonadism. usually presents as part of
APS1 = APECED, autoimmune polyendocrinopathy, candidiasis, and ecodermal dystrophy.
Chronic mucocutaneous candidiasis occurs first, at a young age. Before 4 years. By years 4-5, hypoparathyroidism emerges, followed by Addisons (adrenal insufficiency)
CMC: - Oral candidiasis – Candidal esophagitis esophageal stricture or squamous cell carcinoma – Perianal candidal eczema – intestinal mucosal candidiasis – Infection of skin of the hands ,face and nails – Candidal vulvovaginitis (after puberty)
