Today in report, we spoke about primary vs secondary adrenal insufficiency, workup and treatment of hypercalcemia, and diabetes insipidus. I thought we’d touch on a few fun facts of each endocrinopathy – apologies for the length!
Take Home Points: Adrenal Insufficiency, Hypercalcemia, DI
Adrenal Insufficiency – Symptoms of Primary vs Secondary/Tertiary
Primary AI – adrenal gland failure of cortisol production
- Acute adrenal crisis: hypotension/shock (90%), abdominal/flank/back pain (86%), lethargy, fever (66%), anorexia, n/v (47%), confusion or disorientation (42%), abdominal tenderness or rebound tenderness (22%)
- Chronic adrenal insufficiency: hyperpigmentation (POMC is the ACTH precursor that cleaves into ACTH and melanocyte stimulating hormone, so hyper-secretion of ACTH means higher levels of MSH), GI symptoms, weight loss
- In both, will see electrolyte abnormalities due to mineralocorticoid loss: hyponatremia, hyperkalemia. Hypoglycemia less common in primary AI unless patients are also infected or fasting.
Secondary (pituitary failure of ACTH production) and Tertiary AI (hypothalamic failure of CRH production)Similar symptoms to primary AI with the exception of:
- Hyperpigmentation not present, since ACTH is not hyper-secreted
- Mineralocorticoid function is preserved so:
- Hyponatremia may be present, but due to increased vasopressin secretion from low cortisol (ie – more water, not less salt)
- Hypovolemia and hyperkalemia are not seen
- Hypoglycemia is more common in secondary AI
- May see loss of other anterior pituitary hormones in some causes of secondary AI (FSH,LH,TSH,Prolactin, GH)
Hypercalcemia – Common Causes and the Mechanisms Behind Them
Primary hyperparathyroidism – most often due to an adenoma
- Mechanisms – increased bone resorption, increased kidney absorption, increased gut absorption.
- Mechanisms – PTHrP (squamous cell CA, renal CA, bladder CA), osteolytic metastases (breast CA, MM), tumor production of 1,25-dihydroxy Vit D
Granulomatous dz – sarcoidosis, tuberculosis, histoplasmosis, coccidiomycosis
- Mechanism – converts 25-hydroxy Vit D to 1,25-dihydroxy Vit D →increased Ca gut absorption
Drugs – thiazide diuretics, lithium, vitamin D toxicity, vitamin A toxicity
- In lithium, mechanism is increased secretion of endogenous PTH with resultant hypercalcemia
- Mechanism – ingestion of large quantities of calcium and an absorbable alkali).
- Mechanism – thyroid hormone mediated increase in bone resorption
- Mechanisms – increased bone resorption, volume contraction, increased prox tubule Ca reabsorption
Familial hypocalciuric hypercalcemia
- Mechanism – AD inherited defect in calcium sensing receptor on parathyroid gland –> high/normal PTH in setting of mild hyperCa –>effect on kidney is to increased tubular Ca and Mg absorption
ESRD leading to tertiary hyperparathyroidism
- Mechanism – longstanding PTH stimulation in ESRD (secondary hyperparathyroidism, usually with hypocalcemia) leads to autonomous secretion of PTH by the gland, leading to hypercalcemia
Diabetes Insipidus – Distinguishing Causes of Polyuria
Polyuria = >3L UOP/day. Should consider primary polydipsia, central diabetes insipidus, nephrogenic diabetes insipidus (excluding osmotic diuresis in hyperglycemia and hypercalcemia).
- Primary Polydipsia– increased intake of water, seen in psychiatric disease or conditions that affect hypothalamic thirst center (ex:sarcoid). ADH levels are appropriately low.
- Central DI– deficiency in ADH secretion from posterior pituitary. Etiologies include idiopathic, traumatic, post-surgcal, or ischemic related injury to AHD producing cells. Rarely familial, with later onset of symptoms. ADH levels are inappropriately low.
- Nephrogenic DI– decreased renal responsiveness to ADH. Apparent in varying degrees. Presenting in childhood -> due to inherited receptor V2 or aquaporin-2 channel defects. Presenting in adulthood -> acquired most commonly from hypercalcemia or chronic lithium use. ADH levels are normal.
Differentiating etiology – Water restriction +/- DDAVP while monitoring UOP and osms.
- Corrects w water restriction –> primary polydipsia
- Corrects w DDAVP administration –> central DI
- Does not correct with either –> nephrogenic DI