What is secondary adrenal insufficiency? | ACTH deficiency
Acquired (iatrogenic - sudden cessation of exogenous cortisol/ treated Cushing's after adenoma removal/ hypopituitarism/ isolated ACTH deficiency)
Inherited causes (isolated defect in TPIT mutation (promoter of POMC)/ post-translational defect processing POMC to ACTH by prohormone convertase 1 or 2 (PC1/2 mutation)/ POMC gene mutation (red hair pigmentation due to decreased MSH) |
What are the clinical features of secondary adrenal insufficiency? | Symptoms of cortisol deficiency, in newborn hypoglycemia and failure to thrive, for adults progressive weight loss and anorexia and generalized fatigue
Adrenal mineralocorticoid impaired
No hyperpigmentation |
How is the evaluation of secondary adrenal insufficiency? | Moring serum cortisol <3 / stimulation synacthan test. |
What is primary adrenal insufficiency? | Addison's disease (adrenocortical insufficiency due to dysfunction of adrenal cortex, decreased mineralo and glucocorticoids)
onset of disease occurs when 90% of both adrenal cortices are destroyed |
What are the signs and symptoms of primary adrenal insufficiency? | Hyperpigmentation (due to increased ACTH and POMC secreting MSH), weakness, fatigue, poor appetite, weight loss, dizsiness, myalgia, joint pain, salt craving, amenorrhea
In acute adrenal crisis (nausea vomiting and vascular collapse, fever, maybe comatose, hypotension, hypoglycemia |
What are the causes of primary adreal insufficiency? | Autoimmune adrenalitis (70-90% -isolated or polyglandular)
Infectious (20% - TB/fungal/HIV)
Metastatic cancer (10%)
Adrenal hemorrhage, drugs, others (ALD/AMN/ congenital adrenal hyperplasia) |
What is the workup of primary adrenal insufficiency? | ACTH stimulation test, autoantibody testing (21-hydroxylase Ab)
Abdominal CT (see enlargement of infectious cause and see if both adrenal affected)
Management (corticosteroid and fludrocortisone replacement therapy) |
What is SIADH? | Continued secretion of ADH despite normal or increased plasma volume, impaired water excretion, and thus water retention, hyponatremia (<135), hypo-osmolality (<280) and high urine osmolality |
What are the signs and symptoms of SIADH? | May or may not cause symptoms.
Slow hyponatremia may lead to fewer symptoms than rapid
Severe or rapid-onset hyponatremia cause confusion/ delirium/ disorientation.
generalized muscle weakness, myoclonus, tremor, asterix, ataxia, Cheyen-stokes respiration, coma, seizures... |
How is the diagnosis of SIADH? | There is no single lab test confirmatory of it.
Hyponatremia with hypoosmolality, continued renal excretion of sodium, urine less than maximally dilute, no volume depletion, absence of other causes of hyponatremia (adrenal insuffiency or hypothyroidism) and correction of hyponatremia by fluid restriction
(It is a dx of elimination- tested by dehydration) |
What are the etiologies of SIADH? | Nervous system disorders (psychosis, cavernous sinus thrombus, cerebrovascular accident, lupus, encephalitis, head trauma, meningitis, MS...)
Neoplastic disorder (Lung carcinoma, GI carcinoma, pancreatic and colon, adrenocortical carcinoma, prostate and ovarian)
Pulmonary disorders (bronchitis, ARDS, asthma - this is why we do an X ray or a CT) |
What drugs cause SIADH? | Antidepressants (citalopram, escitalopram, venlafixine..)
Anticonvulsants (carbamazepine, phenytoin, valoproate)
Antipyschotic (risperidone, haloperidol, quetiapine)
Cytotoxic meds (cyclophosphamite)
Pain meds (tramadol, pregabalin, duloxetine) |
What are labs done for SIADH dx? | Serum electrolytes, plasma osmolality, urea (hypouricemia), glucose, urine osmolality, cortisol, TSH, ADH (not very much), maybe brain imaging to see if tumor..) |
Explain urinary Na+ excretion in SIADH? | Loss of Na+ is continuous despite hyponatremia, which should turn off ADH
but here it can't supress it (inappropriately elevated urine osmolality) |
What are the treatment options of SIADH? | Fluid restriction (first line)
Stop meds causing it
Low dose loop diuretics / oral sodium chloride/ eat salt
Demeclocyclin / vasopressin antagonists. |