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“It is not stress that kills Addison, it is the absence of reaction to it.”
2.1 Disorders of the Anterior Pituitary Gland (Adenohypophysis)
Abbreviations: GHRH, growth hormone releasing hormone; GH, growth hormone; IGF-1, insulinlike growth factor-1; Prl, prolactin; ACTH, adrenocorticotropic hormone; FSH, follicle-stimulating hormone; GH, growth hormone; GnRH, gonadotropin-releasing hormone; LH, luteinizing hormone; TSH, thyroid-stimulating hormone.
Hormone secreted by anterior pituitary gland
Pituitary adenoma producing the hormone in excess is called the following
GTA, my favorite video-game (Grand Theft Auto)
2.1.1 Common Features of All Pituitary Adenomas
As pituitary gland is near to the optic chiasm, pituitary adenomas cause compressive visual field defects, which primarily involve the temporal fields causing bitemporal hemianopsia
Large adenoma can compress surrounding pituitary tissue, causing pressure atrophy and hypopituitarism. This leads to sequential loss of anterior pituitary hormones. Growth hormone (GH) and gonadotrophin-releasing hormones (GnRHs) are affected earlier in the disease course, followed by thyroid-stimulating hormone (TSH) and adrenocorticotropic hormone (ACTH).
• Children commonly present with stunted growth due to early development of GH deficiency.
In adults, deficiency of GnRHs (luteinizing hormone [LH] and follicle-stimulating hormone [FSH] deficiency) is more problematic. Men commonly present with impotence and women with amenorrhea.
An adenoma can be functioning (secreting a hormone in excess, as above) or nonfunctioning.
A large functioning pituitary adenoma can present with signs of excess of one of the pituitary hormones and deficiency of other pituitary hormones. For example, a large somatotroph adenoma can present with acromegaly and central hypothyroidism/ hypocortisolemia.
2.1.2 Prolactinoma (Lactotroph Adenoma)
Background: Benign tumor that autonomously secretes prolactin hormone. It is the most common tumor of the pituitary gland.
Pathophysiology/presentation: Excessive secretion of prolactin stimulates mammary glands and also decreases GnRH secretion, causing hypogonadism (decreased LH/FSH production) and the following clinical effects
Development of low estrogen/progesterone state and its complications, such as osteoporosis, oligomenorrhea/amenorrhea, etc.
CCS: 40-year-old female presents with milky breast discharge and oligomenorrhea.
CCS: 55-year-old male presents with decreased libido and impotence. Physical exam reveals visual defects primarily involving bitemporal visual fields.
Work-up: First SIM is to check serum prolactin level and rule out the following conditions that can increase prolactin secretion.
Order qualitative beta-human chorionic gonadotropin test
Check TSH level
Medication side effect
Dopamine directly inhibits prolactin secretion. So, medication that either block dopamine receptors (e.g., metoclopramide, typical antipsychotics) or deplete dopamine (α-methyldopa) can increase prolactin secretion
If the above conditions are ruled out and serum prolactin level is high, NSIDx is MRI of the pituitary gland.
Treatment is indicated in any degree of hypogonadism (e.g., amenorrhea) or in patients with bothersome galactorrhea.
Treatment of choice is pharmacologic. Use cabergoline, which has fewer side effects than bromocriptine. (Dopamine agonist decrease prolactin hormone secretion and shrink tumor size.)
Surgical treatment (removal of adenoma) is done when patients fail to respond to medical management. Note that even in patients with significant neurologic symptoms, medical treatment should be tried first.
Radiotherapy is considered when medical and surgical treatments fail.
A 35-year-old male presents with gynecomastia and decreased libido. He also gives hx of longstanding issues with constipation and cold intolerance. Exam reveals mild decrease in bitemporal visual acuity. He is found to have low TSH and high serum prolactin level. MRI shows pituitary enlargement.
What is the likely dx?
What will be the dx if the patient had elevated TSH instead, along with high serum prolactin level? (Low-yield question; a little bit harder to answer).
2.1.3 Acromegaly and Gigantism
Etiology: Excess GH (Growth Hormone) secretion occurs most commonly from a tumor in the pituitary gland. Other rare causes are ectopic GH or GH-releasing hormone secretion from cancers.
When excess GH secretion occurs in:
It results in:
Gigantism: occurs when growth plates have not fused
Acromegaly: occurs when the growth plates have already fused.
Presents with bony and soft tissue overgrowth—enlargement of hands and feet, coarsening of facial features, thickening of skin folds, and enlargement of mandible (protruded jaws)
Most of the internal organs are also enlarged
Other associated findings are hypertension (HTN), impaired glucose tolerance, diabetes mellitus, entrapment neuropathy (e.g., carpal tunnel syndrome), and osteoarthritis
Most common cause of death is cardiovascular disease
First SIDx: measure insulin-like growth factor-1 (IGF-1) level aka somatomedin. Somatomedin (IGF-1) is a substance secreted by liver in response to GH. This is a great surrogate marker for GH level.
If IGF-1 level is elevated, NSIDx is glucose suppression test. GH levels are measured before and after patient ingests 100 g of glucose. Normally, glucose load should suppress GH secretion. Nonsuppressible GH level confirms diagnosis of autonomous GH secretion.
NSIDx is brain MRI to locate the tumor.
Treatment of choice is surgical (transsphenoidal resection of pituitary adenoma).
Medical treatment is indicated in patients who are at high risk for surgery or when surgical therapy fails. Use somatostatin analogues (octreotide or lanreotide) +/- cabergoline, a dopamine agonist (both inhibit GH release). If still not controlled, use pegvisomant—a somatomedin antagonist that blocks somatomedin (GH) receptors.
Radiotherapy is considered when medical and surgical treatments fail.
Management steps for various pituitary adenomas
Tests to be performed in the following order
Treatment (given in order of preference)
Thyroid-stimulating hormone, pregnancy test, and serum prolactin level1 → MRI brain
Medical therapy → surgery → radiotherapy
Insulin–like growth factor-1 levels1 → oral glucose load test → MRI brain
Surgery → medical therapy → radiotherapy
In all endocrinology cases, when excess hormone secretion is suspected, first step in management is to check the hormone level. Imaging studies are done only after laboratory confirmation of high hormone levels.
Cushing’s disease will be discussed in adrenal section of this chapter.
Pathophysiology: Various pathologic processes can involve the pituitary gland and cause hypopituitarism—autoimmune, infectious, trauma, tumor compression, metastasis, infiltrative (sarcoidosis and hemochromatosis), postsurgical removal of pituitary adenoma, etc. Additional causative scenarios include the following.
Pituitary gland can be affected by
Which may occur in the following situations
Postpartum pituitary necrosis aka Sheehan’s syndrome: CCS – patient with hx of severe postpartum bleeding now presents with inability to lactate
Postpartum pituitary hypophysitis (autoimmune destruction of pituitary gland)
or pituitary macroadenoma: patients usually have bitemporal visual field defects
Clinical features of deficiency
NSIDx (Next step in dx)
LH & FSH
Females: decreased libido, oligomenorrhea/ amenorrhea and anovulation (infertility)
Males: impotence, decreased libido, loss of hair, etc.
Serum LH & FSH
Children: delayed height development
Adults: nonspecific symptoms, such as fatigue and reduced muscle mass
NSIDx is IGF-1 level
Features of hypothyroidism
Fatigue, decreased appetite, weight loss, etc.
Serum cortisol, ACTH, and cosyntropinb stimulation test
a Insulin-induced hypoglycemia was used as a provocative method in the past, but it can be a very uncomfortable experience for the patient, so it is no longer used.
b Cosyntropin is a recombinant ACTH.
Abbreviations: ACTH, adrenocorticotropic hormone; FSH, follicle-stimulating hormone; GH, growth hormone; GnRH, gonadotropin-releasing hormone; IGF-1, insulin–like growth factor-1; LH, luteinizing hormone; TSH, thyroid-stimulating hormone.
Hormone replacement. Replace cortisol before replacing thyroid hormone. If thyroid hormone is replaced before cortisol, this will increase the requirements for cortisone and precipitate a hypoadrenal crisis.
2.1.5 Pituitary Apoplexy
Background: Patients with large pituitary adenoma can develop pituitary apoplexy, an acute clinical syndrome caused by either hemorrhage and/or infarction of the pituitary gland.
Presentation: Hemorrhagic form usually presents with sudden severe headache (“thunderclap” headache) +/- signs of meningism. Look for rapidly worsening visual deficits (due to pressure on optic chiasm).
This may be followed by symptoms due to essential hormone deficiency. Predominant feature is hypotension due to acute adrenal insufficiency.
Management: It is a medical emergency. NSIM is IV fluids and IV hydrocortisone.
2.1.6 Posterior Pituitary Lobe (aka Neurohypophysis)
Posterior pituitary secretes antidiuretic hormone (ADH aka vasopressin) and oxytocin.
ADH promotes reabsorption of free water from the kidneys and maintains serum sodium concentration and plasma osmolarity.
Increased ADH secretion leads to increased total body water resulting in decreased serum Na+ concentration.
2.2 Disorders of Sodium Hemostasis and Antidiuretic Hormone of Posterior Pituitary Gland
2.2.1 Diabetes Insipidus
Pathophysiology: Diabetes insipidus (DI) is either due to deficiency of ADH or resistance to ADH effect. This results in excretion of excessive amount of diluted urine by kidneys, resulting in loss of free water. The resulting polyuria is usually accompanied with compensatory polydipsia.
Central DI is due to absolute ADH deficiency
Various pathologic processes that can affect the posterior pituitary and cause central DI are: autoimmune, infectious, trauma, tumor compression, metastasis, infiltrative (sarcoidosis and hemochromatosis), postsurgical removal of pituitary adenoma, etc.
Nephrogenic DI is due to kidneys’ resistance to ADH
The causes of nephrogenic DI can be many: medications (e.g. lithium, amphotericin B), sarcoidosis, amyloidosis, polycystic kidney disease, hypercalcemia, hypokalemia, etc.
Presentation: Usually patients with polyuria have intact thirst mechanism, so if they lose 20 L of water, they will drink 20 L of water continuously replenishing the free water loss. In situations where thirst mechanism is impaired (sedatives, altered mental state) or if there is a problem with access to water (long car ride, incarceration), patients can become acutely ill, dehydrated, and may develop acute hypernatremia.
Differential diagnosis of diabetes insipidus
Work-up: NSIDx is serial measurements of urinary and plasma osmolarity (after water deprivation, followed by ADH administration) as shown below.
1,2 Exogenous ADH will not have effect, as ADH is already working at maximum after water deprivation.
3 In psychogenic or drug-induced polydipsia the concentrating ability of kidneys gets impaired. It may take days, after normalizing water intake, for the concentrating ability of kidneys to come back to normal.
4 To differentiate nephrogenic DI from central DI, administer desmopressin (an ADH analogue). More than 50% increase in urine osmolarity after desmopressin indicates ADH deficiency (central DI).
Table representation of the graph above
What happens to urine osmolarity after giving desmopressin
Psychogenic or drug-induced polydipsiaa
aIn psychogenic/drug-induced polydipsia, both plasma osmolarity and urine osmolarity is low.
bLow urine osmolarity despite high plasma osmolarity points towards DI.
Abbreviation: DI, diabetes insipidus.
Management of central/nephrogenic DI:
Address the underlying cause.
First step in treatment is to decrease solute intake (low salt and protein diet). This decreases polyuria. (In DI, the kidneys lose the ability to concentrate urine. With fixed urine osmolarity, urine output is primarily determined by amount of solute intake and solute content in urine.)
Second step is to use hydrochlorothiazide (HCTZ) in patients with persistent polyuria. (Diuretics induce a state of partial volume depletion, which increases proximal sodium and water absorption, leading to less delivery of water to distal ADH-sensitive areas.)
Desmopressin is used for central DI, if decreased solute/protein intake and/or HCTZ treatment fails to control polyuria, or if symptoms are severe.
Nonsteroidal anti-inflammatory drugs (NSAIDs) (e.g., indomethacin), which increase renal concentrating ability, can also be used as an adjunct.
For lithium-induced DI, amiloride is the drug of choice.
Likely cause of polyuria + polydipsia in various settings
Polyuria + polydipsia +…. ↓
Likely diagnosis (dx)
Uncontrolled diabetes mellitus (glucose-induced diuresis)
Fatigue + muscle weakness
Hypokalemia-induced nephrogenic DI
Constipation+ abdominal pain
Hypercalcemia-induced nephrogenic DI
Diabetes insipidus or psychogenic/drug-induced polydipsia
Free water loss due to diabetes insipidus.
Hypotonic fluid loss without water replacement
Fluid loss from skin, due to burns or excessive sweating (fever, vigorous exercise, hot weather, etc.).
Fluid loss from gastrointestinal tract, due to osmotic diarrhea (e.g., lactulose ingestion) and diarrhea in infants. (Note: In adults, diarrheal fluid is isotonic.)
Fluid loss from kidneys, due to osmotic diuresis (e.g., diabetic ketoacidosis [DKA], hyperosmolar nonketotic coma [HONK], or drugs such as mannitol).
First step is to look for coexistent volume depletion.
If blood pressure is low (systolic BP ≤ 90 mmHg) and/or heart rate is high (> 90-100 beats per minute), 1st SIM is IV normal saline.
If euvolemic, use IV hypotonic fluids such as 5% dextrose solution in water or if coexistent mild volume depletion is present, use 5% dextrose half normal saline.
The rate of correction of chronic hypernatremia should not exceed > 10 to 12 mEq/L per day, otherwise cerebral edema may develop. For acute hypernatremia of less than 48 hours’ duration, more aggressive correction can be done (1-2 mEq/L correction per hour).
First step is to find out if serum sodium is truly low: Is it true or is it pseudohyponatremia?
aDo direct lab measurement of osmolarity, which might be different from calculated plasma osmolarity.
bIn true hyponatremia, measured plasma osmolarity should be low.
cHypertriglyceridemia and hyperproteinemia can cause a decrease in measured serum Na+ level (pseudohyponatremia) with no change in directly measured plasma osmolarity. This is an artefactual issue.
dHigh serum glucose level decreases measured serum Na+ level (pseudohyponatremia) and increases plasma osmolarity.
In these conditions, development of hyponatremia is a poor prognostic sign. Level of hyponatremia parallels the severity of the underlying condition. Treatment includes restriction of sodium/ water intake and diuretics.
Measure urine Na+ level to differentiate renal fluid loss from extrarenal fluid loss (if source of fluid loss is not clinically evident).
Urinary Na+ > 20 mmol/L= renal fluid loss
Diuretics (prescribed or surreptitiously ingested): thiazide-like diuretics are common perpetrators (e.g., HCTZ, metolazone)
Salt-losing nephropathies, for example, Fanconi syndrome, or acute tubular necrosis (diuretic phase)
Urinary Na+ < 20 mmol/L = extrarenal fluid loss
Patients develop hyponatremia due to compensatory increase in ADH/ aldosterone secretion generally with increased free water intake
GI losses (diarrhea, vomiting, etc.)
Skin losses (burns, toxic epidermal necrolysis, etc.)
Addison’s disease (loss of aldosterone and cortisol hormone)
Urine Na+ > 20 and/ or urine osmolarity > 300
Despite hyponatremia and low serum osmolarity, kidneys are still inappropriately concentrating urine
Urine Na+ < 20 and/ or urine osmolarity < 300
Psychogenic polydipsia: hx of drinking > 15-20 L of water per day
Beer potomania is due to significant intake of beer. Beer is poor in solutes and sodium, but high in calories, thus it suppresses hunger and reduces intake of other foods (and solute)
Tea and toast diet: some patients (particularly elderly) who have poor social support may resort to eating only simple foods like breads, crackers and water, which do not need to be cooked, but have very low salt content
Management of true hyponatremia
Severity (normal serum Na+ is 135-145 mEq/L)
NSIM along with free water restriction and treatment of underlying cause ↓
Free water restriction only
121 to < 130 mEq/L with mild symptoms (mild confusion, fatigue, gait disturbance, nausea, vomiting, etc.)
Directed toward underlying etiology:
If hypovolemic—normal saline
In SIADH—salt tablets (1st step), +/- loop diuretics (induces ADH resistance) +/- vaptansa
In hypervolemic states—diuretics (such as Lasix), +/- vaptansa
≤ 120 mEq/L and/or severe symptoms (e.g., severe confusion, coma, seizures, respiratory arrest)
Hypertonic salineb +/- desmopressin to prevent rapid correction of sodiurmc
aVasopressin receptor antagonist (tolvaptan, conivaptan, mozavaptan, etc.) can be used adjunctively in SIADH and hypervolemic states.
bHypertonic saline is also indicated in acute symptomatic hyponatremia that develops within 24 hours (even if symptoms are only mild).
cRate of sodium correction should not be faster than 0.5-1 mEq/L per hour. Rapid overcorrection may result in central pontine myelinolysis (osmotic demyelination), which usually presents with focal neurological deficits like the ones seen in pontine hemorrhage or infarction (severe cases might present with quadriplegic locked-in-syndrome). (See Chapter 10, Neurology for further details).
Remember the numbers 120 and 130 for degree of hyponatremia.
2.2.4 Syndrome of Inappropriate Secretion of ADH
Etiology: SIADH can be caused by multiple processes, such as trauma, infection, malignancy (especially in lung or brain, e.g., lung injury, head injury, pneumonia, encephalitis, small cell cancer) and medications.MRS-1 Important association to remember is small-cell lung cancer.
Pathophysiology Excessive ADH secretion leads to excessive free water reabsorption and hyponatremia.
Treatment: Its treatment is directed toward underlying condition and also depends upon the severity of hyponatremia and symptoms (see table for management of true hyponatremia). Demeclocycline (ADH receptor blocker) is not commonly used nowadays because of increased risk of nephrotoxicity and high cost.
MRS-1 Drugs that can stimulate secretion of ADH (Tip: most of the drugs start with “C”)
vinCristine and vinblastine.
Antidepressants SSRIs (Citalopram, sertraline, etc.), Tricyclic antidepressants
How to find out the cause of hyponatremia?
First step is to look at volume status
Urine Na+ (mmol/L)
Extrarenal fluid loss
Renal fluid loss
Syndrome of inappropriate antidiuretic hormone secretion
Psychogenic polydipsia, beer potomania, or tea and toast diet
3. A 45-year-old female has serum sodium of 112 mEq/L and altered mental status. What is the NSIM?
2.3 Disorders of Calcium Hemostasis and Parathyroid Gland
2.3.1 Basics of Calcium (Ca2+) Metabolism
Total serum calcium = bound calcium + free calcium.
Bound form: Calcium is a positively charged ion which binds to albumin and other negatively charged compounds (e.g., citrate–, PO4 –, SO4 –).
Free form is the one that is biologically active and closely regulated by parathyroid hormone (PTH).
The two hormones that regulate calcium are PTH and Vitamin D.
Requires hydroxylation in liver and kidney to become biologically active
Signals osteoblasts to activate osteoclasts. Osteoclasts then start dissolving bone, thereby decreasing bone density and in the process release more calcium and phosphorus into the blood
Signals the kidneys to increase reabsorption of Ca2+ and excretion of PO4 –
Signals the intestinal epithelial cells to increase
Final effect is ↑ Ca2+ and decreased PO4 – 1
Final effect is ↑ Ca2+ and ↑ PO4 – 1
If calcium and phosphorus are in opposite directions, think PTH related and if they are both in same direction, think vitamin D related.
Patients with hypoalbuminemia (due to liver cirrhosis, protein-losing enteropathy, malnutrition, etc.) can have the following issue with calcium mechanics:
– Decreased total calcium but normal free Ca2+ level. These patients are asymptomatic.
Standard chem-7 or basal metabolic profile (BMP) tests measure total calcium. Hence if serum albumin is low, the calcium needs to be corrected with the help of a formula using serum albumin. We don’t need to know this formula for boards.
A case of masked hypercalcemia:
I had once taken care of a patient, who didn’t have a primary care doctor, who presented with fatigue. Complete metabolic profile revealed high normal calcium level and very low serum albumin. Corrected calcium value was found to be more than 14. She ended up having a diagnosis of severe acute hypercalcemia due to parathyroid adenoma. Hypoalbuminemia was probably a result of severe malnutrition due to hypercalcemia associated gastrointestinal symptoms.
2.3.2 Disorders of Calcium Metabolism
For the tables below, cover the diagnosis column (right most column) and try to explain mechanism of calcium disorder. Again, let us reiterate an important point—If calcium and phosphorus are in opposite directions, think PTH related; if they are both in same direction, think vitamin D related.
↑ /or high Na
N or lowb
NSIDx is 24-hour urinary calcium.
Elevated urinary Ca2+ = primary hyperparathyroidism (parathyroid adenoma or hyperplasia)
Low urinary Ca2+ = familial hypocalciuric hypercalcemia (discussed later in section of primary hyperparathyroidism)
N or lowb
PTH-related peptide (PTHrP) secreted from cancer cells (squamous cell cancer of lung, breast cancer, etc.). This peptide works just like PTHc.
Overproduction of calcitriol (vitamin D) from lymphomas or Granulomas (e.g., in sarcoidosis or generalized granulomatous infection) (glucocorticoids are effective in this form of hypercalcemia)
Excessive vitamin D intake
N or ↑
Consider causes that increase bone resorption—prolonged immobilityd, multiple myeloma, hyperthyroidism. (Look for elevated alkaline phosphatase)
aIn hypercalcemia, PTH should be low if feedback mechanism is intact.
bDue to negative feedback from hypercalcemia.
c Hypercalcemia of malignancy can be due to PTHrP secretion (typically by squamous cell carcinoma) or due to cytokines secreted by osteoclastic metastatic cells (multiple myeloma is a classic example). Cancers at times can cause both types (e.g. breast cancers).
dPatients who have high bone turnover rate (e.g., Paget’s disease or in children), immobilization can lead to development of significant hypercalcemia (Hypercalcemia of Immobilization).
Abbreviation: PTH, parathyroid hormone
Primary hypoparathyroidism (Etiology: DiGeorge syndrome, thyroidectomy complication, parathyroidectomy, polyglandular autoimmune syndrome, etc.)
Chronic renal failurea
Vitamin D deficiency (osteomalacia in adults and ricketsc in children)
N or ↑
Vitamin D resistant ricketsd
aIn renal failure, there are two primary mechanisms: (1) retention of PO4 2 (which chelates calcium), (2) decrease in vitamin D production.
bLooks like it is a PTH-related disorder with calcium and phosphorus in opposite direction. Calcium is low even though PTH is high. So, PTH must not be working at all. Dx is pseudohypoparathyroidism, where there is a defect in PTH receptor, so even if PTH is present, it does not exert its effect.
cFor rickets, look for frontal bossing, bowed legs, and enlargement of costochondral junction.
dPrimary pathology is defect in vitamin D receptors, so even though vitamin D level is normal or high there is lack of effect.
e ↑ = secondary hyperparathyroidism (Elevated alkaline phosphatase is present in all cases except in pseudohypoparathyroidism.)
A pediatric patient presents with frontal bossing, bowed legs, and enlargement of costochondral junction.
Hereditary hypophosphatemic ricketsa
An old patient’s x-ray shows diffuse thinning of bone.
aHeritable disorder in which the primary problem is significant phoshaturia (phosphate wasting).
Miscellaneous info on calcium-related disorders:
Hydrochlorothiazide can cause mild serum hypercalcemia by increasing urinary calcium reabsorption. This hypocalciuric effect is helpful in prevention of stone formation in hypercalciuric recurrent calcium phosphate stones.
Differences in clinical features of hyper-/hypocalcemia
Constipation, fatigue, lethargy, muscle weakness, cardiac arrhythmias, etc.
Blunts ADH signaling pathway which may lead to nephrogenic diabetes insipidus (polyuria, polydipsia)
Muscle cramps, paresthesia, tetany, cardiac arrhythmias, etc.
Abbreviation: PTH, parathyroid hormone.
Hypercalcemia Clinical features
Gastrointestinal: constipation, abdominal pain, pancreatitis, etc.
Neurological symptoms depending upon severity: difficulty concentration → fatigue, weakness → altered mental status → seizures, coma.
cardiac: arrhythmias can also occur.
Normal serum calcium is ≤ 10.2 mg/dL
aFurosemide (Lasix) is not routinely indicated in management of hypercalcemia. If patients develop volume overload with IV normal saline, it can be judiciously used.
b Bisphosphonates decrease osteoclastic activity. As opposed to calcitonin, it takes at least few days for the hypocalcemic effect to kick in, but it is more sustained. It is contraindicated in severe renal failure.
Bisphosphonates are also indicated in patients with symptoms related to bone resorption, for example, patient with acute back pain due to metastatic osteolytic lesion.
Denosumab is an alternative treatment of persistent hypercalcemia of malignancy refractory to bisphosphonates.
cIV calcitonin is mostly recommended in patients with serum Ca2+ > 14. It decreases calcium levels faster than bisphosphonates do, but its efficacy is reduced after 48 hours. In severely hypercalcemic patients, hemodialysis can be done as a treatment of last resort.
Etiology: MCC is parathyroid adenoma. Other causes include parathyroid hyperplasia/ malignancy.
Workup: After detecting elevated calcium levels, NSIDx is to check serum PTH level.
If elevated or upper side of normal range, NSIDx is 24-hour urinary calcium measurement. If 24-hour urinary calcium is elevated the dx is primary hyperparathyroidism.
Management of Primary Hyperparathyroidism
a Symptomatic hypercalcemia is an obvious indication. In asymptomatic patients, the following are indications for surgery:
Young patients < 50 years of age with no comorbidities, who have low risk for surgery
Calcium phosphate renal stones, nephrocalcinosis or 24-hour urinary calcium > 400 mg/day
Serum calcium level of 1 mg/dL or more above the upper limit of normal
Reduced renal function (eGFR < 60 mL/minute)
bOther options are CT or MRI scan of parathyroid gland. Localization of tumor is not necessary in patients undergoing nonsurgical management.
cA potential complication of removal of parathyroid adenoma is hungry bone syndrome. (7 to 10 days after surgery with precipitous decline in PTH levels, bones can go into a rapid remineralization phase with increased uptake of calcium and phosphates, resulting in serum hypocalcemia and hypophosphatemia. This is usually self-remitting and transient.)
dCinacalcet decreases PTH secretion by activating calcium-sensing receptors in parathyroid glands (it acts by “mimicking” calcium).
The MCC (most common cause) of hypercalcemia in nonhospital outpatient setting is primary hyperparathyroidism.
The MCC of hypercalcemia in hospital setting is malignancy. ”
Hypocalcemia Additional etiologies of hypocalcemia
Multiple units of blood transfusion
Citrate (a negatively charged ion), which is used as an anticoagulant in blood bags, binds with free Ca2+ causing hypocalcemia
Acute hypoxemia (e.g., pulmonary embolus) or panic disorder with increased respiratory rate
Respiratory alkalosis: in alkalosis, there is depletion of positively charged ions (e.g., H+ion) and abundance of negatively charged ions (e.g., HCO3 –). Hence, Serum albumin becomes more negatively charged, and more free Ca2+ binds with albumin, decreasing the free calcium level
Patient is an alcoholic or is malnourished
Hypomagnesemia inhibits PTH secretion
This is due to loss of cholecalciferol (vitamin D)-binding protein in urine
Presentation: Acute hypocalcemia leads to generalized neuromuscular and cardiac hyperexcitability.
Management: Treatment of acute hypocalcemia is with IV calcium gluconate or calcium chloride. Maintenance is with oral calcium.
Potassium-calciummagnesium and QT interval always go in opposite directions. If potassium, magnesium or calcium is low, QT interval is prolonged.
2.4 Thyroid Hormone
Thyroid hormone controls the basal metabolic rate and Na+–K+–ATPase pump in all our cells.
In hyperthyroidism, everything is fast
In hypothyroidism, everything is slow
Weight loss despite increased appetite (due to increased basal metabolic rate)
Weight gain despite decreased appetite (due to decreased basal metabolic rate)
Heat intolerance due to increased basal metabolic rate and increased intrinsic heat production (even minimal external heat makes patients uncomfortable)
Diarrhea due to increased GI motility
Increased deep tendon reflexes
Slow deep tendon reflexes, slow speech and movement
Excessive production and expression of β1 adrenergic receptors leads to increased β1 adrenergic activity = sweating, tachycardia, anxiety, and tremors
The drug of choice to control these symptoms is β blockers
Additional features: sparse hair, croaky voice, puffy looking face, and myxedema
Note: Both hypo- and hyperthyroidism can cause proximal muscle myopathy.
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