on the endocrinology ward two individuals came in the first person is 47 year old melania whom recently went through a surgical procedure called thyrodectomy due to thyroid cancer melania came in with tetany and on the clinical examination there was a positive vostek sign the other person is 55 year old emma who came in with constipation muscle weakness and bone pain she has a history of kidney stones specifically calcium stones and she also said that she's been feeling down lately calcium phosphate and pth levels were taken in both individuals melania had low levels of calcium high levels of phosphate and low levels of pth whereas emma had high levels of calcium low levels of phosphate and high levels of pth both individuals seem to have a problem in their parathyroids first a bit of physiology the four parathyroid glands are on the posterior of the thyroid gland and their main job is to keep blood calcium levels stable changes in the body's levels of extracellular calcium and phosphate levels are detected by the surface receptor in the parathyroid's chief cells both decreased calcium levels and increased phosphate levels can signal the chief cells to release more parathyroid hormone or pth pth affects many organs in the bones it binds to osteoblasts the bone building cells and causes them to release rank ligands or rank l along with monocyte colony stimulating factor or mcsf these will cause osteoclast precursors to mature into osteoclasts which break down bones and release calcium and phosphate into the blood pth also gets the kidneys to reabsorb more calcium and excrete more phosphate it also activates calcitriol also known as 125 dihydroxycolcalciferol or active vitamin d active vitamin d then goes on to cause the gastrointestinal tract to increase calcium absorption altogether these effects help to increase extracellular levels of calcium when they're low now let's talk about hypoparathyroidism where there's an abnormality with the parathyroid glands so pth levels are low the most common cause is removal of the parathyroid glands during thyroid or parathyroid surgeries another cause is an autoimmune condition that destroys parathyroid glands there are also genetic causes like degeorge syndrome which causes a variety of immune and birth defects with degeorge syndrome the third and fourth pharyngeal pouches don't develop so the parathyroid glands and thymus that originate here will be missing in the infant then there's pseudohypoparathyroidism where pth levels are normal or high but the kidneys and bones don't respond to pth which is called pth resistance an example is pseudohypoparathyroidism type 1a or albright hereditary osteodystrophy which is an autosomal dominant condition the cause is a mutation in the gs protein alpha subunit and this mutation is inherited from the mother gs proteins function as cellular signaling proteins and where there's a defect in the alpha subunit in this case the pth receptor in the bones and kidney won't be able to activate and so pth cannot exert its effects with albright osteodystrophy classical symptoms include shortened fourth and fifth digits short stature obesity and developmental delay now there's also pseudo-pseudohypoparathyroidism which is a subtype of albright's hereditary osteodystrophy and it also includes symptoms like brachydactyl developmental delays and short stature however the gene is passed on by the father instead of the mother and there's no pth resistance so there's normal pth and calcium levels now let's look at the symptoms caused by low levels of parathyroid hormone or the lack of response to them both will lead to hypocalcemia and hyperphosphatemia which results in more excitable neurons this can lead to tetany or the involuntary contraction of muscles the spontaneous firing of neurons leads to bostec sign which is when facial muscles twitch after the facial nerve is lightly tapped usually one centimeter below the zygomatic process it can cause trousseau's sign which is where a blood pressure cuff applies pressure on the brachial nerve which is enough to make it fire resulting in a muscle spasm that makes the wrist and metacarpophalangeal joints flex if the hypocalcemia and hyperphosphatemia are severe this can lead to life-threatening complications like severe seizures and cardiac arrhythmias let's move on and talk about hyperparathyroidism there are three types of hyperparathyroidism primary secondary and tertiary in primary hyperparathyroidism the parathyroid gland is responsible for the protein because it makes parathyroid hormone independently of the calcium level most often primary hyperparathyroidism is caused by a parathyroid adenoma a benign tumor rarely primary hyperparathyroidism is caused by hyperplasia where parathyroid cells divide excessively causing growth of the glands and in very rare cases there can be a carcinoma of the parathyroid glands the symptoms of primary hyperparathyroidism can be remembered especially for exams as stones thrones bones groans and psychiatric overtones now hyperparathyroidism causes hypercalceuria which can lead to dehydration and can stimulate the formation of calcium-based kidney stones and gallstones thrones refers to the toilet to remind you of the polyurea or frequent urination that results from impaired sodium and water reabsorption bones is for bone pain that results after chronic hormone-driven demineralization in order to release calcium groans is for constipation and muscle weakness both of which are partly due to decreased muscle contractions the excess calcium makes neurons less excitable which leads to slower muscle contractions and diminishes neuron firing in the central nervous system as a result there are psychiatric overtones which refers to symptoms like depression and confusion in addition excess pth will cause osteoclasts to break down bone and makes the kidneys hold on to calcium and get rid of phosphate resulting in hypercalcemia and hypophosphatemia eventually bone resorption by osteoclasts can lead to a condition called osteitis fibrosis cystica where there are cystic bone spaces that are filled with osteoclasts and hemosiderin and they're called brown tumors classic signs include subperiosteal erosions that affects the phalanges in the fingers and salt and pepper sign in the skull which refers to the numerous small lesions caused by bone resorption osteitis fibrosis cystica is classically associated with primary hyperparathyroidism but can be seen sometimes with secondary hyperparathyroidism too with primary hyperparathyroidism labs show hypercalcemia hypophosphatemia high levels of pth high alkaline phosphatase or alp due to increased bone resorption and high levels of camp in the urine due to hypercalcemia in secondary hyperparathyroidism the parathyroid gland is normal but it makes excess parathyroid hormone in response to chronic hypocalcemia due to another cause most often the problem is chronic kidney disease where the kidneys cannot excrete phosphate properly or make enough calcitriol the hyperphosphatemia reduces the amount of free calcium ions in the blood by binding with them and the lack of calcitriol means less calcium is absorbed by the intestine secondary hyperparathyroidism can present with symptoms of chronic kidney disease as that is often the underlying cause other secondary hyperparathyroidism symptoms include bone resorption called renal osteodystrophy and calcification in blood vessels and soft tissues because the high levels of phosphate stick to any available calcium forms bone-like crystals that deposit in different tissues labs show hypocalcemia hyperphosphatemia low levels of vitamin d as well as high pth levels usually above 50 picograms per milliliter and high alp levels tertiary hyperparathyroidism is basically a situation where individuals who have had secondary hyperparathyroidism for many years develop primary hyperparathyroidism specifically parts of the parathyroid gland start making parathyroid hormone independently of blood calcium levels resulting in hypercalcemia labs show really high levels of pth and hypercalcemia another condition is familial hypocalciuric hypercalcemia or fhh this is a genetic disorder caused by defective calcium sensing receptor in the parathyroids and the kidney these receptors are less sensitive to calcium levels in the blood so the parathyroids might overproduce pth when the kidneys cannot sense calcium levels they will increase calcium reabsorption leading to hypocalceuria and hypercalcemia the elevated pth and hypercalcemia might make you think of primary hyperparathyroidism but the key difference that fhhh causes hypocalciuria while primary hyperparathyroidism can have normal or hypercalceuria fhhh is typically benign and the person will be asymptomatic all right as a quick recap problems with the parathyroid gland can cause hypo or hyperparathyroidism which leads to calcium imbalance the most common cause of hypoparathyroidism is removal of the parathyroid glands during thyroid or parathyroid surgeries other causes include autoimmune and degeorge syndrome all of these lead to decreased pth levels and hypocalcemia next there's pseudohypoparathyroidism type 1a or albright hereditary osteodystrophy and this is caused by pth resistance in the bones and kidneys this also causes hypocalcemia but pth levels are increased finally we have pseudo-pseudohypoparathyroidism where there's the same bone deformities and developmental problems as albright hereditary osteodystrophy but the pth and calcium levels are normal symptoms and signs of hypocalcemia include tetany positive vostek and truso signs moving on to hyperparathyroidism primary hyperparathyroidism is most often caused by a single parathyroid adenoma but can also be caused by hyperplasia and carcinoma of the parathyroids all of which increases pth release the symptoms of primary hyperparathyroidism can be remembered as stones thrones bones groans and psychiatric overtones over time osteitis fibrosis cystica can develop labs will show increased pth hypercalcemia and hypophosphatemia familial hypocalceuric hypercalcemia will also have hypercalcemia and sometimes moderately elevated pth but there will be hypocalceria in secondary hyperparathyroidism the parathyroid gland makes excess parathyroid hormone in response to chronic hypocalcemia like in chronic kidney disease labs show hypocalcemia hyperphosphatemia low levels of vitamin d as well as high pth levels tertiary hyperparathyroidism is basically a situation where individuals who have had secondary hyperparathyroidism for many years develop primary hyperparathyroidism labs show really high levels of pth and hypercalcemia back to our cases melania came in with tetany and positive vostek sign both suggesting hypocalcemia labs showed hypocalcemia hyperphosphatemia and low pth based on history symptoms and signs and labs melania is suffering from hypoparathyroidism probably caused by the recent removal of her thyroid which also removed the parathyroid glands emma came in with constipation and muscle weakness as well as bone pain she also has a history of kidney stones and lately she has been feeling low suggesting she might be depressed all of these signs stones bones groans and psychiatric overtones suggest primary hyperparathyroidism which is then confirmed by the labs hypercalcemia hypophosphatemia and high levels of pth imaging studies of the parathyroids were done and a pth secreting adenoma was found helping current and future clinicians focus learn retain and thrive learn more you