1 - (4 hours) 27.09.23 - Endocrine Disorders.pdf

Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Endocrine Disorders Endocrine disorders, focus on thyroid. Hypothalamus and pituitary diseases Hypothalamus is found in the encephalon, connection between 2 cerebral hemispheres and it's the best connection between endocrine and NS....

Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Endocrine Disorders Endocrine disorders, focus on thyroid. Hypothalamus and pituitary diseases Hypothalamus is found in the encephalon, connection between 2 cerebral hemispheres and it's the best connection between endocrine and NS. 1 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Endocrine and nervous system in the body. The hypophyseal is divided in two portion: 1) Adeno → real glandular part 2) Neurohypophysis has best connection with nervous system The hypophysis is a very small gland (few cms), found in the sella turcica. The connection between the hypothalamus and the hypophysis relates in the fact the former produces releasing factors in the portal vessels connecting the adenohypophysis to the hypothalamus. These act on specific cells which secrete and produce the factors that are then transmitted to the rest of the body. While, considering neurohypophysis, in fact it does not produce hormones. Hormones stored in the hypothalamus: - ADH - regulation of hydrosaline balance and thirst - Oxytocin - regulation of uterine contraction ⇒ produced by neurosecretory cells in hypothalamus and produce the hormones 2 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 This is just to remind the diff axis. We have in hypothalamus these releasing hormones: - GH → receptors in the liver - Where does the GH have its own receptor? In the liver. Liver cells produce IGF-1. - Please note that somatostatin goes and inhibits GH. TSH-TRH axis T3 and T4 produced by the thyroid gland. The main function is maintenance of the basal metabolism and control the Fertility and … for catecholamines in the heart. This is why we have tachy and brady when altered secretion of the thyroid hormones is present. TRH is also able to activate prolactin and it is a hormone which receives a constant inhibitory stimulus from the dopamine which is in the hypothalamus. Prolactin is able to inhibit GnRH. GnRH-LH/FSH axis GnRH is inhibited by prolactin and it is important in the sexual development as it induces the release of LH/FSH and then sexual hormones. CRH-ACTH-Cortisol axis ⇒ goes and stimulates production of ACTH by adenohypophysis that goes toward the adrenal cortex, for production of cortisol and sexual androgens. Aldosterone does not belong to the hypothalamic-pituitary axis because its production is stimulated by renin. 3 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Adrenal cortex has three diff layers: - Zona glomerulosa which produce aldosterone - Zona Fasciculata for glucocorticoids - Zona Reticularis for sexual hormones The RAAS is activated every time there is a decrease in BP or less sodium, the kidney produces renin, which converts angiotensin and angiotensinogen I. In the lungs ACE2 converts Angiotensin 1 in 2. It has is receptors at the area of the zona glomerulosa of the adrenal gland 42 year old man, bla bla bla, has a pituitary tumor on a ct scan, what's the most common type of pituitary tumor 4 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 A. GH oma B. Prolactinoma C. Non-secreting adenoma D. ACTH oma THE MOST COMMON TYPE OF PITUITARY TUMOR IS PROLACTINOMA. Pituitary Tumors: Adenomas Pituitary tumors classified based on dimensions and functionality: - Microadenoma - Macroadenoma - Functional - Non functional PRL>GH>ACTH>TSH>FSH/LH You can see that prolactinoma is the most frequent followed by GHoma, then …. Clinical features depend on the kind of hormones produced. Main manifestations of prolactinoma: Prolactinemia gives ○ amenorrhea (because it suppresses GnRH production), ○ gynecomastia , ○ erectile dysfunction, 5 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 ○ decreased libido in males GHoma → Gigantism (in child) and acromegaly (in adult) Mass effects: Hypophysis has a superior relationship with optic chiasm. Fibers of chiasm are compressed and there is this typical view by people affected by pituitary adenoma: bitemporal hemianopsia (among first symptoms). Pituitary apoplexy = infarction, often due to rapid growth of an adenoma. The vascular support does not grow as rapidly as the adenoma causing a sort of infarct. Resulting in hypopituitarism. Sheehan’s syndrome: In pregnancy there is an hypertensive peak… 6 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Diagnosis: - MRI with contrast medium - CT scan because of emergency department - Ophthalmologic evaluation → for mass effect - Laboratory investigation → hormones produced, so the exact population Treatment depending on functionality of the adenoma: If it is functioning → Treat Non functioning: ○ Mass effect → treat ○ Asymptomatic → observation can be enough SURGERY preferred: Trans-sphenoidal surgery Endoscope create a hole in sella turcica and aspirate the adenoma Prolactinoma is the only pituitary tumor for which we start with medical treatment with dopamine agonist. crbe; in all the other tumors, except for the prolactinoma, we start with transphenoidal surgery and then we use medical treatment. In prolactinoma the medical treatment is much more effective and we use dopamine agonists because dopamine inhibits prolactin level (see previous slide). Cabergoline and Bromocriptine Bro-mocrytonite (dopamine agonists) Treatment for GHoma = somatostatin analogue (Same reason as prolactinoma and dopamine agonists) 7 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 The first cause of hyperprolactinemia is drug induced like i case of plasil Dopamine agonists decrease prolactin levels. Dopamine antagonists increase prolactin levels: e.g. Plasil, some antipsychotics (risperidone) etc… Sheehan syndrome is an infarction of the hypophysis due to an hypertensive peak happening during labor, thus we cannot have an overproduction → we have hypo-prolactinemia not hyper One of the main consequences of the hypertensive peak is DIC which leads to loss of coagulation factors due to the great use of them in the thrombi formation. 8 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Hyperprolactinemia Hyperprolactinemia: level higher than 20-25 micrograms 1. Confirmation: 2-3 determinations as prolactin can be high due to stress 2. Exclude most frequent etiologies → drugs and physiologic (pregnancy) 3. Exclude comorbidities: a. Primary hypothyroidism: due to the lack of T3-T4, the negative feedback is absent and TSH and TRH are higher and TRH stimulates the production of prolactin. b. Chronic kidney disease: the kidney is not able to excrete prolactin in urine and thus accumulates in blood 4. Pituitary hypersecretion a. Damage to the peduncle: e.g., craniopharyngioma breaks connection between hypothalamus and hypophysis , prolactin can be freely produced by the hypophysis b. Prolactinomas: cut off as 100 to discriminate btw functional and prolactinoma but this is not absolute value. Bromocriptine: possible treatment. 9 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 E : right answer Treatment The only kind of adenoma that we start with medical treatment, if it is ineffective we try surgery and radiation therapy with gamma-knife 10 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Acromegaly Most common cause if pituitary adenoma In adults Clinical features, depending on hyperproduction of GHRH → leads to increased GH and IGF-1 then at liver. Typical phenotype: Frontal bossing CV risk increases due to cardiomegaly (GH leads to growth in the whole body) Diabetes mellitus Colon polyps and tumors (GH and IGF1 favors the onset of colon polyps and tumors) Lab: hyperphosphatemia and hypercalcemia Pay attention to the fact that when we have hypercalcemia associated with acromegaly, we are facing MEN1 which is also called 3P disease: P pituitary P hyperpara pituitarism Pancreatic neuroendocrine tumor: insulinoma 11 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 → 4 is correct answer. Many times patients go to medical attention because of changes in hands, limbs, and cannot write. Buffalo hump (gibbo in italiano) is more connected to Cushing’s syndrome (high levels of cortisol in blood; DD with Cushing's disease which is instead associated with pituitary adenoma) rather than acromegaly. Cushing syndrome caused by p. adenoma is called cushing disease. 12 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Diagnosis: Lab tests: Elevated levels of IGF-1 GH is still high after OGTT, high levels of glucose should suppress GH. High levels of glucose should suppress the GH but if it is not then something is wrong. IGFB3 is also good at discriminating against patients affected by GH hypersecretion. MRI Ophthalmology evaluation Treatment: TNS surgery Medical: ○ Somatostatin analogues: octreotide, these can also be used in neuroendocrine tumors. ○ Pegvisomant → GH receptor agonist. Radiation therapy GIGANTISM is the same thing as acromegaly but it happens in children before epiphyseal closure. It is characterized by: - Acanthosis nigricans because of skin thickening - Carpal tunnel syndrome because … 13 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Hypopituitarism Pituitary adenomas can also lead to hypo conditions: - Hypothalamic tumors - CNS tumors It is a life threatening condition sometimes when it's acute. Our body has a mechanism for which we start losing hormones from the least useful to the most useful: We start losing GH → LH/FSH → TSH → ACTH Cortisol is the most important and the last one to be lost because it regulates stress, important at the level of the heart, DNA synthesis, anti inflammatory drugs lowering the immune defenses o f the body. It is the last hormone we lose in hypopituitarism, but the first one we need to reintroduce during treatment. In children ALWAYS, in adults we need to determine the clinical scenario. 14 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Neurohypophysis 2 most important hormones : - Oxytocin → stimulation of muscular uterine cells but also “love” hormone (promotes social interaction)…) AND SO ON - Vasopressin → important in the regulation of hydrosaline balance ADH It has its own receptors in the level of the nephrons, in the distal tubule in the collecting duct. AQP are the ones allowing water to move from the tubule to the blood. The two main disease related to ADH: SIADH= Syndrome of inappropriate production of ADH → often due to paraneoplastic syndrome, usually due to a small cell lung cancer. Urine will be in small volumes, very concentrated, hyperosmolar, while urine gets very concentrated. We should use diuretics to treat this condition, in particular Tolvaptan that acts directly on aquaporins. 15 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Diabetes insipidus: AQP do not work anymore which causes water to pass constantly in urines. There are 2 types of diabetes insipidus: ○ Central → not enough production of ADH ; possible etiology trauma or hypothalamic tumors ○ Nephrogenic → ADH is produced but it cannot bind to aquaporin → problem at the level of the nephron; TTT vasopressin. 16 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Thyroid Diseases Thyroid gland is organized in follicles. In the thyroid we have diff types of cells: - The epithelial cells are responsible for the production of T3 and T4. - Also the colloid that stores iodide used for the synthesis of these hormones. - Among follicular cells we have parafollicular cells that produce calcitonin → called because of these C cells. Thyroid carcinoma associated with high levels of calcitonin is the medullary thyroid carcinoma. 1. Through dietary iodide in seafood and salt → goes in the bloodstream and follicular cells → Receptor. 2. There is an internalization of iodine through iodine symporter. 17 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 3. Iodide is then brought to the apical part of the cell, oxidized by TPO and coupled with thyroglobulin. 4. 5. Endocytosis of colloid Leads to internalization of iodide and the synthesis of thyroglobulin. Later iodide couples with tyrosine on thyroglobulin with formation of MIT and DIT. Later on will bind T3 and T4 and after endocytosis through proteolysis there is the formation of the hormones etc. In the blood, T3 and T4 travel bound to thyroid binding protein and transthyretin The thyroid gland is highly vascularised, it has 4 arteries and they are all branches of the EXTERNAL carotid artery. 18 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 For the venous system we have 6 veins: - 2 superior → from the internal jugular vein - 2 middle to the internal jugular vein - 2 inferior → form the brachiocephalic trunk Most common cause of primary hypothyroidism in Europe and US is Hashimoto thyroiditis. Iodine deficiency is the most common cause world wide, if you take into account developed countries it is Hashimoto. Thyroid diseases are more common in women. Clinical features Classic symptoms: ○ Bradycardia ○ Cold intolerance ○ Weight gain 19 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Others (very rare): ○ Macrocytic anemia (macrocytic) bc thyroid hormones stimulate Hb production, ○ dementia ○ Hyponatremia ○ Pericardial, pleural effusion This is the typical facies of a woman affected by hypothyroidism. Nowadays it’s not so common anymore bc pts are treated earlier. Edema of the tongue, typical of hypothyroidism. Diagnosis: Hypothyroidism = increased TSH levels If subclinical it can happen that T3 and T4 are still normal Do you treat subclinical hypothyroidism and if yes when? When symptoms arise. - If TSH levels are 10, you treat 20 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 In case of hashimoto you have to look for antibodies: anti TPO (oxidase Iodide) and Anti thyroglobulin (protein from which hormones derive) The treatment is to replace the hormone missing, the thyroxine T4 is much more produced than T3. Ratio of production is 20:1 = T4:T3 Since T3 is the metabolically active hormone, at the periphery there is a deiodinase enzyme that transforms T4 into T3. Since the life of the drug is longer than T3, we give T4. Aim = getting the normal levels of TSH. PPI should be taken at night, not in the morning as these may interfere with L-thyroxine absorption Non-fasting intake may alter its absorption so if we need to take in the morning thyroid hormones, breakfast can be consumed after at least 1 h. Atrophic gastritis DOES reduce the absorption of L thyroxine. 21 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Hyperthyroidism and Thyrotoxicosis Hyperthyroidism = Overproduction of thyroid hormones. Thyrotoxicosis = High levels of TH in bloodstream, it can depend on external assumption of TH The most frequent etiology is graves disease Grave basedow is an autoimmune disease Toxic multinodular goiter is a condition in which pts who have lifelong nodules and at a certain points there is the formation of goiter leading to hyperthyroidism. Clinical presentation Main features of Graves: Symptoms of hyperthyroidism: ○ tachycardia, ○ hot intolerance, ○ weight loss ○ sweating ○ HT ○ Hot weather intolerance ○ Weight loss Exophthalmos is typical and also raphe sign: failure of upper eyelid to follow the movement of the eye(?) Which can be another cause of hyperthyroidism? The TSHoma, a pituitary adenoma secreting TSH. But it’s not as common as acromegaly and prolactinoma. 22 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Diagnosis Hyperthyroidism generally means low levels of TSH and high levels of thyroid hormones. In the case of graves you have to look for the typical abs. If we find these Abs in the bloodstream we have a diagnosis If you don't find them you have to perform a thyroid scintigraphy. In only few cases (10-15%) also anti TPO and anti TG may be associated with Graves disease but always with hypothyroidism. Treatment Thyroid hormones are able to work together with catecholamines in the heart. So, we can use beta blockers for symptomatic treatment, beta blockers, non-selective. A possibility is Inderal, propranolol It is also used for Bleeding of esophageal varices beaside for hypertension, migraine Anti thyroid drugs to disrupt the thyroid: propylthiouracil (not in Italy). In Italy we use methimazole. However, since methimazole is teratogenic we cannot use it in the 1st trimester of pregnancy → switch to it in the 2nd and 3rd trimester 23 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 We can also use symptomatic therapy, so glucocorticoids. Iodine If the drugs are not effective for 1/1 year and a half we should use other treatments like radioactive iodine therapy or surgery: we start with antithyroid drugs, then if these are not effective choose between radioactive iodine therapy and surgery. Radioactive iodine therapy is contraindicated in children and pregnancy and pts undergoing this therapy should be isolated. Surgery: thyroidectomy. Good especially in elderly. Important side effects: surgical risk (thyroid is highly vascularized). Hypocalcemia: parathyroid glands are removed as well, so if we do not have PTH production, we lose the possibility to raise Ca levels in blood. Recurrent laryngeal nerve lesions leading to dysphonia or vocal cord paralysis. Graves Basedow in B Pregnancy gives this condition (diffuse hypercaptation of the thyroid) bc during the first 8 weeks of pregnancy there is the production of Hcg. It has 2 subunits. The alpha subunit is similar to TSH, FSH and LH → during the first trimester of pregnancy it can mimic the TSH → at scintigraphy we have diffuse uptake in the thyroid C toxic multinodular goiter: strong uptake in different points. D. Plummer adenoma → uptake in a single point E. thyroiditis, metastases etc → no uptake 24 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 D is the correct answer. Improving the ophthalmological picture is the consequence. We are treating the overproduction of Th and the symptoms associated with it Thyroiditis 25 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Thyroiditis is an inflammation of the thyroid gland. The correct answer is D. This is the histology for De Quervain, multinucleated giant cells. We can distinguish between painful and painless thyroiditis. Painful ○ acute and suppurative thyroiditis usually associated with bacterial infections. Treatment is with antibiotics In case of acute thyroiditis we have thyroid symptoms concomitant with bacterial infection. If bacteria it is neutrophilic leukocytosis ○ Subacute or De Quervain thyroiditis associated with a viral infection Usually we recognize lymphocytosis in the subacute antibiotics can be used just to avoid infection, but the tt is with NSAIDs ex: Brufen, so antiinflammatory drugs. After 1-2 weeks the pt could have an enlarged thyroid, dysphagia etc. Painless thyroiditis 26 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Is usually associated with auto abs, the erythrocyte sedimentation rate is usually normal. In Riedel thyroiditis the normal tissue of the thyroid is replaced by fibrous tissue. Woody or Riedel is the only one with surgical indication. Clinical course of acute thyroiditis: overproduction of thyroid hormones, but it is not a real overproduction, hormones are released just because the gland is disrupted. After this there is a phase of hypothyroidism. At the beginning you use propranolol, NSAIDs etc. Then in hypothyroidism we use Levothyroxine. After 3 months the situation is usually solved; the only exception if Hashimoto which leads to hyperthyroidism after a while A pt going to the physician after a flu syndrome a few weeks earlier , now with dysphagia. A clear case of De Quervain thyroiditis. 27 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 So only symptomatic treatment with NSAIDs. She will recover within 3-4 months, and only rare cases will need to use levothyroxine The only thyroiditis that leads to permanent hypothyrdoim is Hashimoto; all the other pts recover in 3-4 months. Subacute thyroiditis. Basic clinical presentation: after a flu- fever- jugular swelling. 28 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Hashimoto bcs is chronic and so with lymphocytic infiltration which is typical. Lymphocytic thyroiditis is a synonym for Hashimoto. 29 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Thyroid Nodules If TSH is low → hyperthyroidism → we perform scintigraphy and we find a hot nodule. If at US or palpation you find thyroid nodules you have to find out the nature of these nodules. Hot nodules usually benign( multinodular goiter or Basedow Graves disease)instead if it's cold go for FNA bcs can be malignant. Anyways before FNA make evaluations, most of the time observation is enough. When do we perform FNA? We have to consider risk factors: previous radiation tt, familiarity for thyroid cancer. If they are present FNA is done. If no risk factors are present and the nodules are very small we go for observation. 30 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 If a nodule is warm, we suspect multinodular goiter or Graves disease. EUTIRADS is the European classification that we use to classify the nodules. 1 - no nodules 5 - high risk ith FNAC highly recommended because of high risk of these being malignant Bad features for nodules are: - Irregular shape - Irregular margins - Calcifications - Intra Nodular vascularisation After FNAC we have the TIR classification for the cytology: TIR 1 → not diagnostic so repeat the examination; if T1C still means not malignant. TIR 2 → benign 31 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 TIR 3 → follicular/undetermined: we do not know fi the follicular one is an adenoma or a carcinoma ○ 3A → low risk, we follow up. ○ 3B→ High risk → extemporary biopsy during surgery TIR 4 → suspected malignant → surgery TIR 5 → malignant This classification is very good for papillary thyroid cancer but not for medullary. We don't know if the follicular one is an adenoma or a carcinoma. As a general rule from 3B on it is a malignant node. Thyroid cancer Thyroid cancer We have 2 types of cells: Follicular and parafollicular Epithelia. Anaplastic → worst prognosis From the parafollicular epithelium we have the medullary carcinoma Calcitonin is the marker for parafollicular medullary carcinoma. 32 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 The papillary and follicular are luckily the most frequent cancers and they have a good prognosis. We perform total thyroidectomy or radioactive ablation And then the suppressive T4 bc TSH promotes both the production of thyroid hormones and the enlargement of the gland. This external T4 reduces TSH production, and there is no stimulus for thyroid gland growth. To avoid the enlargement of the thyroid gland we give T4. Medullary: It's related to MAN II A and B syndrome. It has an important genetic component: the RET (?) genes are associated with medullary thyroid cancer. Calcitonin and Amyloid (recognized with congo red staining) are the markers of medullary carcinoma, also CEA. We perform total thyroidectomy. After thyroidectomy the pt can undergo hypothyroidism so we provide T4 replacement In this case the marker is calcitonin as well as CEA. Anaplastic: worst one especially for elderlies; all features of malignancy at histo like increased mitosis, nucleoli, etc. Local invasion is very frequent. Growth of these tumors leads to suppression of respiration or digestion, leading to death even before metastasis development. 33 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 They may die in 6 months. We have just palliative care. Lucky it is the least frequent tumor. MEN I is a 3 “p” syndrome: Parathyroid Pancreas Pituitary Menin: Autosomal dominant MEN 2 MEN 2A → primary hyperPTH If calcium levels are not increased it is a MEN2B. 34 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Calcium-Phosphorus Homeostasis Main characters of calcium and phosphorus homeostasis are : Vitamin D that promotes bone formation mainly. In the kidneys it leads to calcium and phosphorus resorption. In the gut vit D leads to Ca and P04 absorption. Vit D leads to: Increases Ca and P The pth leads to bone resorption → There is an increase in the level of calcium in blood. PTH increases Ca and lowers P levels Calcitonin by parafollicular cells leads to bone formation and Ca elimination in the kidneys → hypocalcemia (but in very small amounts). 35 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 This is to say that on the Skin we have Pre-vit D or we take vit D from food (milk, orange juice or fish) In the liver there is the first hydroxylation, in position 25. Then in the kidneys there is the second hydroxylation (1,25) and can promote growth of muscle, bone health, etc. In case of hypovitaminosis D, in the absence of other illnesses, what do we give to pts? The 25 hydroxyl vit D. If the pt has CKD or hypoparathyroidism, we directly give this. We can also give it in hypo parathyroidism. If we have hypoPTH, Vit D cannot be activated and … it cannot be activated (?) IV administration of calcium is also used also in the screening and follow up of medullary tumors to see if there is an increase in calcitonin. 36 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 PTH Conditions of hypoCA lead to increase in PTH which leads to a decrease in P levels and it also leads to a Ca increase. PTH acts its action at level ok kidneys in collecting tubules bc it has its receptors PTHR1. In the kidneys it activates this channel that leads to the passage in the blood. Hypercalcemia stops the passage of urine from kidneys cells to the blood on the other hand. Hypercalcemia = plasma calcium above 10.5 37 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Primary hyperthyroidism = hyperfunctioning of parathyroid, like tumor or hyperplasia. In hospital setting hypercalcemia is alway bad thing because is due to bone metastasis or paraneoplastic syndrome. PTH related peptide if from squamous cell lung cancer Granulomatous diseases produce vit D themselves and this leads to increased Calcium. Bone metastasis → high calcium in blood→ lowe PTH. 38 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 The typical symptoms of hypercalcemia: Diagnosis is with findings of hyperCa with hypoP and high PTH When do we treat ? - young - kidneys stones, kidney damages - If the pt wants to go surgical intervention 39 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Primary → high PTH, high CA (consequence of high PTH), low P Secondary (problem is not in the PT glands. Parathyroid is activated as a consequence of another problem) → high PTH, low/nrmal Ca, high/nomral P. One cause of this can be Chronic kidney disease, bc kidneys cannot excrete phosphate anymore, excreting just calcium → so high levels of PTH. Tertiary — condition in which CKD ha activated Parathyroid glands to produce elevated pth levels and after. A while pth can compensate for the low levels of calcium so after a while we can fine hypercalcemia and hyperparathyroidism 40 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Case: pt with hypercalcemia -> saline solution 0.9% Before we need to fill the pt with fluids, then we need to empty him It makes no sense to give directly the diuretic ti the pt, bc if the pt is empty → no urine. So we have to feed the pt and then give diuretics. Diuretics we gives are loop diuretics (lasix=furosemide) THIAZIDE leads to hypercalcemia in fact it is used in the prophylaxis of kidney stones. Loop diuretics promote Ca excretion (FUROSEMIDE- LASIX) Then furosemide. We can also use IV biphosphonate and in the end glucocorticoids that can potentiate the hypocalcemic effect of calcitonin, but these are the last option to use. 41 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 OSTEOPOROSOS: not use methylprednisolone, with is a corticosteroid that has as major side effect OP. Osteoporosis: It is a decrease in bone mass and increased risk of fractures. Quantitative and qualitative alteration of bone tissue. It can be primary or secondary. Especially in postmenopausal women bc of decreased levels of estrogen and increased bone resorption Senile esp Multifactorial → in older patients you don't have much sun exposure, decreased physical activity etc. Females usually have primary forms due to decrease in estrogens. Males usually have secondary forms, the most important is glucocorticoid osteoporosis. Normal value of non density in DEXA is 2.5 to -1 Below -1 is osteopenia Below -2.5 is osteoporosis (?) 42 Lesson 1 - 4 hours - Prof.ssa Crudele - 27 September 2023 Two main systems that lead to increased alkaline phosphatase when damaged are the liver and bones. ALP is always increased in bone and liver diseases, so in hypoparathyroidism is not elevated. In hypo parathyroidism we have the contrary Osteosarcoma: increased AKP bc destructed bone Vit D and calcium if levels are low 1. Anti resorptive Bisphosphonates DMAb: denosumab that inhibits RANK-L, so inhibits osteoclast activity Slow bone resorption means inhibition of osteoclasts. 2. Anabolic stimulate new bone formation. The only one is teriparatide but it’s not used anymore because it leads to osteosarcoma. 3. Romosozumab is a MoAb that inhibits sclerostin. Antiresorptive and anabolic action 43