Thread: Endocrine Pharmacology

ENDOCRINE PHARMACOLOGY



GROWTH HORMONE (GH):

• ANABOLIC EFFECTS:
  • Increases amino acid uptake into tissues.
  • Enhances protein synthesis.
• CATABOLIC EFFECTS:
  
  • Antagonizes insulin after it's been around for some time: impairs glucose uptake and promotes lipolysis.
  • GH can thus be Diabetogenic for people with Diabetes.

THYROID HORMONE:

• Synthesis of Thyroid Hormone: Thyroglobulin is synthesized in the Thyroid follicular cells and secreted into the lumen of the follicles.
  • Iodide is taken into the thyroid follicular cells from the general circulation, and it is transcytosed to the apical membrane.
    • This transport occurs by active Na+-Cotransport
  • ORGANIFICATION: The process of iodinating the thyroxines, forming MIT and DIT, and then forming T3 and T4.
    
    • On the outside of the membrane, in the lumen, peroxidase catalyzes the oxidation of iodide and its attachment to Thyroglobulin, forming Mono-iodothyronine (MIT) and di-iodothyronine (DIT).
    • MIT and DIT then join to form T3 and T4
    • This process is blocked by the Thionamides
• Biological Effect:
  
  • Tri-iodothyronine (T3): Formed by joining MIT + DIT
    • It is far more potent and has the principal biological effects: increase transcription at target cell, and exhibit negative feedback at pituitary.
    • Very little of it (5µg / day) is released from the Thyroid. The rest is made by converting T4 ------> T3 in the peripheral blood.
    • T3 is carried, in part, by TBG in the blood. However, T4 binds more tightly to TBG than does T3.
  • Thyroxine (T4): Formed by joining DIT + DIT
    
    • It is far less potent than T3. It has little biological effect in itself and is more of a "pro-hormone."
    • It is released, in quantity, by the Thyroid, where it then binds to TBG in the blood. It is slowly converted to T3 in the periphery.
    • It binds more tightly to TBG then does T3.
    • It has a longer half-life, so it sticks around longer than T3.
• HYPOTHYROIDISM: Myxedema.
  
  • TYPES:
    • PRIMARY HYPOTHYROIDISM: Deficiency of Thyroxine itself. Goiter is present, due to increased TSH.
      • TSH will be high and T4 will be low.
      • TRH Test: Give TRH, and TSH will show a hypersensitive response and shoot way up.
    • SECONDARY HYPOTHYROIDISM: No goiter is present.
      
      • TSH will be low and T4 will be low.
      • TRH Test: Give TRH, and TSH will remain low and show little or no response.
    • TERTIARY HYPOTHYROIDISM:
      
      • TSH is low, initially, and T3 is low.
      • TRH Test: Give TRH, and TSH will show a delayed response before it finally kicks in and increases somewhat.
  • Cretinism: Childhood hypothyroidism, which leads to retarded growth and mental retardation if not treated.
  • CAUSES:
    
    • Idiopathic
    • Hashimoto's Thyroiditis
    • Treatment of Hyperthyroidism with radio-iodine, 131I.
  • SYMPTOMS: Weakness, shallow respiration, puffy face, frowsy hair.
• HYPERTHYROIDISM: Thyrotoxicosis.
  
  • SYMPTOMS: Hypertension, tachycardia, hypermetabolism, irritability
  • Thyroid Storm: Acute hyperthyroid crisis, which can be deadly.
  • CAUSES:
    • Grave's Disease: Auto-immune stimulation of TSH receptors. You do see exophthalmos.
    • Toxic Nodular Goiter: There is no exophthalmos.
  • TREATMENT:
    
    • Thionamides: Inhibit organification of iodine.
      • Has a delayed effect, because thyroglobulin stores must first be used up before the effect is seen.
    • Ionic Inhibitors: Inhibit uptake of iodine.
    • Surgery
    • Radio-iodine, 131I: Diffusely kills thyroid cells. Resulting in eventual and inevitable hypothyroidism.
    • Iodide: Temporarily (early on) inhibits proteolysis of thyroglobulin, preventing freeing of thyroxine. Effect wears off. Used to treat Thyroid Storm.
      
      • Often given in preparation for an operation, as it makes the thyroid gland firm and shrink up.

ADRENAL HORMONES:

• MINERALOCORTICOID SYNTHESIS: 21beta-Hydroxylase is required for synthesis.
  • Cholesterol ------> Pregnenolone ------> Progesterone
  • Progesterone ------> 11-Deoxycorticosterone (21beta-Dehydroxylase)
  • 11-Deoxycorticosterone ------> Corticosterone ------> Aldosterone
• CORTICOSTEROID SYNTHESIS: 21beta-Hydroxylase, 17alpha-Hydroxylase and 11beta-Hydroxylase are required for synthesis.
  
  • Cholesterol ------> Pregnenolone
  • Pregnenolone ------> Progesterone ------> 17alpha-Hydroxyprogesterone (21beta-Hydroxylase, 17alpha-Hydroxylase)
  • 17alpha-Hydroxyprogesterone ------> 11-Deoxycortisol
  • 11-Deoxycortisol ------> Cortisol (11beta-Hydroxylase)
• SEX HORMONE PATHWAY:
  
  • Cholesterol ------> Pregnenolone ------> Dehydroepiandrostenedione (DHEA) ------> Androstenedione ------> Testosterone
  • Testosterone ------> Estradiol (Aromatase)
  • Estrogen <====> Estriol <====> Estradiol <====> Estrone
• 21beta-Hydroxylase Deficiency: You see reduced Cortisol ------> excess ACTH ------> adrenal hyperplasia.
  
  • You also see a buildup of the metabolic precursors.
    • Buildup of progesterone and 17alpha-hydroxyprogesterone
    • Buildup of Androstenedione ------> lots of androgens hanging around ------> feminine virilization.
  • TREATMENT: Cortisol will relieve the ACTH and the adrenal hyperplasia, and will replace deficient Cortisol. Sometimes you also have to give mineralocorticoid, but usually there is some residual aldosterone activity.
    

CORTISOL:

• METABOLITES: 17-hydroxycorticosteroids are the metabolic byproducts of Cortisol. They can be measured in the urine, in order to monitor Cortisol levels in the blood.
• REGULATION: Cortisol, ACTH, CRH, negative feedback, etc. etc.
  • CRH: There is a diurnal rhythm of release of CRH, which results elevated levels of Cortisol in the early morning hour.
  • None of the steroids are stored in the adrenals. They are synthesized on demand and released immediately. Lipophilic substances don't easily fit into vesicles!
• INDICATIONS:
  
  • Adrenal insufficiency (Addison's Disease)
  • Inflammatory, non-infectious processes of all sorts: Arthritis (all types), auto-immune diseases, Asthma, diseases of the eye.
• CONTRAINDICATIONS / ADVERSE EFFECTS:
  
  • You must taper off the dose of Cortisol slowly, to allow the patient to adjust. If you withdraw the drug quickly, you will see adrenal insufficiency.
    • ADRENAL ATROPHY: Giving exogenous corticosteroids ------> suppressed ACTH ------> adrenal gland atrophy.
  • Don't use with infections.
  • Because of their side-effects (see Effects below), use with caution in case of Diabetes, CV disease, HTN, psychoses, glaucoma, and osteoporosis.
• EFFECTS:
  
  • ANTI-INFLAMMATORY: Corticosteroids are the most potent anti-inflammatories available.
    • Effects on Protein Synthesis:
      • Cortisol promotes synthesis of proteins called Lipocortins ------> inhibit Phospholipase-A2 ------> inhibit production of arachidonic ------> inhibit leukotrienes and prostaglandins.
      • Cortisol inhibits the protein-translation of Inducible Cyclooxygenase II (COX-II) ------> inhibit prostaglandins and thromboxanes.
    • Physiologic Effects:
      
      • Cortisol has a negative effect on lymphocytes, monocytes, and macrophages. It inhibits release of cytokines, IL-1, IL-2, and IL-6, and TNF-alpha.
        • There is feedback inhibition here, too, because these cells normally have a stimulatory effect on the hypothalamus (CRH) and pituitary (ACTH). When these cells are then inhibited by Cortisol, then the extra stimulus is gone.
      • Reduced migration of inflammatory cells to site of injury.
      • Increased susceptibility to infection.
      • Decreased lymphocyte production.
      • Impairment of DTH (Delayed-Type Hypersensitivity) reactions.
  • PERMISSIVE EFFECTS: The presence of glucocorticoids is required for certain events to take place:
    
    • The actions of catecholamines on smooth muscle (contraction) and on fat cells (lipolysis).
  • TISSUE EFFECTS:
    
    • Inhibit fibroblasts ------> connective tissue loss and thinning of skin.
    • Negative Ca+2 balance ------> osteoporosis.
      • Ca+2 and Vit. D absorption in the intestine is decreased ------> increased PTH ------> Ca+2 is lost from bones.
    • Negative nitrogen balance
    • Cardiovascular effects: Increased blood pressure, heart-rate, and TPR. Cross-reactivity with Aldosterone leads to increased Na+ retention.
    • CNS: Euphoria, psychosis, behavioral changes, lost cognitive function.
    • GI: Increase stomach acid and pepsin production, which can lead to peptic ulcer.
    • Electrolyte balance: Aldosterone cross-reactivity causes higher Na+ and lower K+. This can lead to hypokalemia, salt retention, and metabolic alkalosis.
  • METABOLIC EFFECTS: Basically, hyperglycemia, plus any other effects that would increase the amount of glucose delivered to the brain.
    
    • Gluconeogenesis.
    • Insulin release and glycogen deposition. Glucose use is diverted from the periphery and used centrally.
    • Protein catabolism
    • Uptake of fat by fat cells. Deposition of fat occurs in other places (Buffalo hump)
• CUSHING'S DISEASE: Cushing's disease is Secondary Hypercorticism. ACTH is high in Cushing's Disease.
  
  • Cushing's Syndrome, on the other hand, describes the general cluster of symptoms attributable to adrenal hyperfunction.
  • If ACTH is low and Cortisol is high, then there is probably a steroid producing tumor somewhere, such as in the adrenal gland, or ectopically, in another location. On the other hand, if ACTH levels are high, then it is Cushing's Disease.
  • SYMPTOMS / CHARACTERISTICS:
    • Moon Facies.
    • Redistribution of fat away from extremities toward the center.
    • Buffalo Hump
    • Bruising, poor wound healing, osteoporosis.
    • Increased susceptibility to infection.
    • Hyperglycemia
• ADRENAL INSUFFICIENCY (ADDISON'S DISEASE):
  
  • SYMPTOMS:
    • Weakness, fatigue
    • Weight loss, anorexia
    • Hypotension
    • Hypoglycemia
    • Hyperpigmentation: ACTH is derived from pre-opiomelanocortin, the same precursor that Melanocyte Stimulating Hormone (MSH).
      • High ACTH can show some cross-reactivity with melanocytes, resulting in hyperpigmentation.
  • ACTH Test: Give ACTH and measure Cortisol levels, to distinguish between primary and secondary adrenal insufficiency.
    
    • PRIMARY INSUFFICIENCY: Give ACTH ------> Cortisol levels remain low. Also, you should see normal or high ACTH levels to start with.
    • SECONDARY INSUFFICIENCY: Give ACTH ------> Cortisol levels shoot up.
      • Metyrapone Test: Confirmatory test for secondary adrenal insufficiency. Give Metyrapone to inhibit 11beta-Hydroxylase and therefore inhibit Cortisol synthesis. Normally, this blocking of Cortisol synthesis should result in high ACTH levels. If Metyrapone does not yield high ACTH levels, then we know the problem is secondary.

GONADOTROPINS:

• GnRH: Stimulates release of FSH and LH.
  • EFFECTS:
    • Pulsatile release of GnRH ------> pulsatile release of LH ------> stimulates follicular growth, the luteal surge (via positive feedback effect of estrogen at mid-cycle), and ovulation.
    • Continuous release of GnRH can actually supress the gonadotropins.
  • STRUCTURE: GnRH is a decapeptide. Two analogues have replaced one amino acid (Lys-6) in order to give the structure a longer half-life.
    
    • Leuprolide: Replace Lys-6 with d-Leucine
    • Nafarelin: Replace Lys-6 by a naphthalene-derived Alanine.
  • SECOND MESSENGER: GnRH-Receptors are coupled to the IP3/DAG/Ca+2 second messenger system.
• FSH + LH: They are large molecules and there is no synthetic analogue. They can only be obtained from natural products.
  

ESTROGEN:

• PHARMACOKINETICS: Estrogen is lipophilic, metabolized in the liver, and is recycled through the enterohepatic circulation.
  • It has a high concentration of effects on the liver compared to the periphery.
  • Antibiotics can destroy normal GI flora ------> interfere with enterohepatic recycling of estrogen ------> reduce estrogen levels. This is why oral contraceptives can fail when taken with antibiotics.
• Natural Estrogens: The natural estrogen are not used in oral contraceptives, because they are metabolized
  
  • Estradiol: Most potent. Formed primarily in ovary.
  • Estriol: Less potent. Formed in the liver from estrogen, or in peripheral fat from androstenedione.
  • Estrone: Less potent. Formed in the liver from estrogen, or in peripheral fat from androstenedione.
• POST-MENOPAUSAL THERAPY: Equine natural estrogens are used for post-menopausal therapy.
  
  • BENEFICIAL EFFECTS:
    • Antagonizes the effect of PTH on bone ------> prevent bone loss after menopause.
      • Estrogen does not appreciably add bone mass, but it can prevent bone loss.
    • Increases plasma levels of HDL, and decreases LDL, thus it is effective in preventing heart disease.
    • Even in low doses, it prevents hot flashes associated with Menopause.
  • ADVERSE EFFECTS:
    
    • Post-menopausal bleeding.
    • Nausea
    • Breast tenderness
    • Migraine headaches.
    • Can promote estrogen-dependent cancers, particularly uterine cancer but also breast cancer.
      • If you use progestins along with estrogen, then this risk is completely eliminated.
      • Give estrogen during first 25 days of month, and add progestin during last 10-15 days. Bleeding will result.
• ORAL CONTRACEPTION:
  
  • ESTROGEN ADVERSE EFFECTS: The adverse effects of estrogen are dose-related. They were a bigger deal in the past, because estrogen doses used to be much higher. Today's doses are much lower, and the adverse effects are not as pronounced.
    • Increased synthesis of clotting factors ------> Thromboembolism, stroke, especially in women who smoke.
    • Increased production of liver hormone-binding proteins (CBG, TBG, SHBG) ------> increased circulating levels of Thyroxine, Cortisol, sex hormones.
    • Cholelithiasis
    • Depression
    • Minor effects: weight gain, breast tenderness, nausea
• POST-COITAL CONTRACEPTION: Take extremely high doses of estrogens alone after intercourse. Any of the estrogen would work.
  
  • Mechanism unclear, but they think it disturbs the environment in the uterus, making it unfavorable for implantation.

PROGESTINS: They generally modulate the effects of estrogens (and lessen their side-effects) when used in oral contraceptives.

• EFFECTS:
  • Makes cervical mucous thicker. This is an important effect in contraception, as the thick mucous inhibits movement of sperm and can even be spermicidal.
  • Decreases the endometrial proliferation caused by Estrogen.
• PHARMACOKINETICS: Natural Progesterone is rapidly degraded in liver, thus it cannot be given PO. Synthetic (oral contraceptive) progestins can be given PO.
• ORAL CONTRACEPTIVES:
  
  • Combined Oral Contraceptives: The main reason progestins are added to oral contraceptives is to ensure prompt withdrawal bleeding.
  • Progestins used alone are not as effective (96.5-97%) as combined oral contraceptives (99%).
  • There is no menstruation at all when using progestins alone.
  • Depo-Provera and Norplant are both pure-progestin mixtures.

DIABETES: Diabetes Type I (IDDM)Diabetes Type II (NIDDM)MechanismInsulin is defective or is never formed. Antibodies against pancreatic beta-cells.Insulin resistance; down-regulation of insulin receptors; failure of pancreas to release insulin even though it being formed.SurvivalInsulin is absolutely required for survival.Patient will survive without insulinSynonymsKetosis-Prone Diabetes Juvenile-Onset Diabetes
Ketosis-Resistant Diabetes Adult-Onset Diabetes
OnsetSudden, often discovered by ketoacidosis. Childhood polydipsia, polyphagia, polyuria.Gradual, insidious. Often discovered incidentally, or when chronic complications arise.NutritionOften thin. Failure of action of insulin.Usually obese.KetoacidosisFrequentSeldom or neverTreatment (order of importance)Insulin always required Diet
Never oral hypoglycemics
Diet and exercise Oral hypoglycemics
Insulin

• KETOACIDOSIS: Lack of insulin (i.e. high Glucagon:Insulin ratio) promotes lipolysis, breakdown of proteins, and glycogenolysis.
  • Coma: In hyperglycemia, high sorbitol in plasma ------> dehydration ------> coma.
    • Coma is more often seen with hypoglycemia than with hyperglycemia.
  • TREATMENT:
    
    • Crystalline Zinc Insulin is the most immediate-acting insulin, which is the treatment of choice for acute ketoacidosis.
    • Ketoacidosis is treated with both HCO3- (to relieve the acidosis) and K+ (to replace lost K+ in cells).
      • In Ketoacidosis, there is plenty of K+ in the blood, but the cells are starving for K+ because the patient is dehydrated.
      • When you give the IV insulin, glucose goes into cells, and K+ follows it. We therefore must replace this K+ to avoid hypokalemia.
  • BIOCHEMICAL CAUSE:
    
    • Glucagon promotes Lipolysis ------> lots of Acetyl-CoA in the blood.
      • Acetyl-CoA builds up in liver.
    • Glucagon promotes Gluconeogenesis ------> Oxaloacetate is diverted to work on making glucose and is therefore unavailable for the TCA cycle.
    • Excess Acetyl-CoA cannot be used in TCA cycle and is hence diverted to Ketone Body production.
• HYPOGLYCEMIA:
  
  • SYMPTOMS: Palpitations, sweating, tachycardia, fainting, coma.
  • TREATMENT: IV-Glucose.
  • COMA: Hypoglycemic coma is more common in Diabetic than ketoacidosis coma, due to over treatment with insulin.
    • Give a comatose diabetic IV glucose, until their blood sugar is known for sure. If you give insulin to a hypoglycemic patient, you'll probably kill them!
  • ALCOHOL inhibits gluconeogenesis and thus can lead to hypoglycemia in Diabetics. Alcohol combined with insulin can lead to hypoglycemia.
• EXERCISE: The cornerstone of treatment of Type-II Diabetes.
  
  • It leads to lower blood-sugar and the up-regulation of insulin receptors.
  • It allows for greater penetrance of insulin into muscle tissue, improving the utilization of insulin.
• INSULIN:
  
  • SYNTHESIS: Proinsulin is hydrolyzed to Insulin + C-Peptide
  • SECRETION: Stimulated by Glucose, Vagal stimulation, and some amino acids. Mechanism involves a K+ channel and Ca+2 channel on the pancreatic beta-cell.
    • Fasting State: No glucose is around.
      • ATP is depleted.
      • K+ channels are open.
      • The cell is in the resting, hyperpolarized state.
    • Resting State: Plenty of glucose is around (or vagal stimulation).
      
      • ATP is plentiful.
      • The K+ channel closes.
      • The cell depolarizes.
      • Ca+2-channels open, Ca+2 flows in, and insulin is secreted.
    • Sulfonylureas: They promote insulin release by blocking the K+-channel, such that it is always closed. Hence the cell is depolarized and insulin is released.
  • INSULIN RECEPTOR: It's a Tyrosine Kinase.
    
    • Down-Regulation: Binding of insulin causes aggregation of receptor-subunits, and repeated binding can cause internalization and destruction o-f the receptor. This is one way in which continual insulin stimulation can lead to Type-II Diabetes.
  • ACTION:
    
    • GLUCOSE-TRANSPORTERS: Insulin up-regulates the transport of GLUT4 transporters into the membranes of target cells.
    • LIVER:
      • Insulin promotes glycogenesis
      • Insulin antagonizes glucagonic effects of glycogenolysis, ketogenesis, and gluconeogenesis.
    • MUSCLE: Insulin promotes protein synthesis and glycogenesis.
    • FAT: Insulin promotes fat uptake and storage in adipocytes.
      
      • It stimulates lipoprotein lipase ------> free fatty acids from circulating lipoproteins.
      • Glucose transport and glycolysis generate glycerophosphate, which is needed as the glycerol backbone in triglyceride synthesis.
      • It inhibits intracellular lipase, preventing lipolysis in adipose tissue.
  • TYPES of Therapeutic Insulin:
    
    • Porcine Insulin: Has a better allergy profile than the bovine insulin.
    • Bovine Insulin: Insulin antibodies are formed, but they usually don't hurt anything. They can decrease the effectiveness of the insulin, at which point a different insulin prep can be used.
      • Allergic reaction is possible, usually due to impurities in preparation.
    • Human Insulin: Created by DNA recombination technology. More expensive, and more pure. Use with folks who are allergic to other types.
  • Lipodystrophy: Adverse reaction of hypertrophy or atrophy in the adipose site where injection was given. To prevent lipodystrophy, switch injection sites.
• SULFONYLUREAS: Oral hypoglycemics used to treat Type II Diabetes.
  
  • MECHANISMS:
    • They promote insulin secretion in beta-cells. They block K+ channels on pancreatic beta-cells ------> K+ remain closed ------> beta-cells remain depolarized ------> promote insulin secretion.
    • They antagonize the effects of glucagon.
    • They potentiate the action of insulin in target tissues.
  • CONTRAINDICATIONS:
    
    • Do not use in pregnancy. They cross the placental border. Never use with gestational diabetes.
  • DRUG INTERACTIONS:
    
    • Drugs that neutralize the action of Sulfonylureas:
      • Diazoxide: Inhibits release of insulin.
      • Phenytoin
      • Propanolol
      • Corticosteroids: Leads to "adrenal Diabetes."
    • Drugs that potentiate the action of Sulfonylureas, and thus must be used with care to avoid hypoglycemia:
      
      • Sulfonamides: They displace sulfonylureas from plasma proteins
      • Salicylates: Interferes with urinary secretion.
      • Phenylbutazone: Competition for liver enzymes, plus interfere with urinary excretion
      • Chloramphenicol: Competes for liver enzymes
      • Probenecid: Interferes with urinary secretion.
• COMPLICATIONS of DIABETES:
  
  • MECHANISMS:
    • GLYCOSYLATION of blood proteins
      • Examples of glycosylated proteins: hemoglobin, components of the lens, collagens, myelin.
      • Advanced glycosylation products are formed through time. The initial glycosylations are usually reversible.
    • POLYOL PATHWAY: The way to get rid of excess glucose in non-insulin-dependent tissues, such as the brain.
      
      • Glucose + NADH + N+ ------> Sorbitol + NAD+ (Aldolase Reductase).
      • Accumulation of Sorbitol is believed to play a role in Diabetic retinopathy, nephropathy, neuropathy, and microangiopathy.
  • Major Complications:
    
    • Atherosclerosis
    • Neuropathy
      • Loss of sensation can lead to foot ulcers.
    • Retinopathy
    • Nephropathy
    • Microangiopathy
      

PARATHYROID HORMONE (PTH): It increases serum Ca+2 and promotes resorption of Ca+2 in bone.

• EFFECTS: It increases serum Ca+2 and decreases serum phosphate.
  • BONE: It increases resorption of Ca+2 from bone. It increases osteoclastic activity by promoting the action of osteoblasts.
  • KIDNEY:
    • It increase resorption of Ca+2, Na+, Cl-, and some amino acids.
    • It promotes synthesis of 1,25-(OH)2-Vit-D
    • It increases excretion of PO4-3.
• REGULATION:
  
  • Increased serum Ca+2 inhibits PTH secretion.
  • Increased serum PO4-3 ------> decreased free serum Ca+2 ------> increased PTH secretion.

VITAMIN-D:

• EFFECTS:
  • GUT: Increased Ca+2 and PO4-3 absorption in gut.
  • BONE:
    • 1,25-(OH)2-Vit-D increases resorption of Ca+2 ------> increase plasma Ca+2.
    • 24,25-(OH)2-Bit-D may increase deposition of Ca+2 into bones (i.e. osteoblastic activity)
  • KIDNEY:
    
    • Increases reabsorption of Ca+2 ------> higher blood Ca+2
    • Increases reabsorption of PO4-3 ------> higher blood PO4-3.
• SYNTHESIS: It is promoted by PTH.
  
  • SKIN: Cholesterol ------> Cholecalciferol is a non-enzymatic cleavage catalyzed by UV-Light.
  • LIVER: Form Calcifediol. 25-Hydroxylase puts a hydroxyl group on the side chain.
  • KIDNEY: Form Calcitriol. 1alpha-Hydroxylase puts a hydroxyl at the 1alpha position.
• ADVERSE EFFECTS:
  
  • Hypervitaminosis D = Vitamin D toxicity, characterized by hypercalcemia and nephrocalcinosis.

This article is from http://www.geocities.com/doctor_uae/....htm#endocrine

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