CAH is a disorder of steroid biosynthesis, most often due to a deficiency of the enzyme 21-hydroxylase. Without the enzyme, the adrenal gland cannot conserve:Select one:a. salt properly, leading the baby to lose saltb. ADHc. sugar properly, leading the baby to lose sugard. testosterone

A 6-day-old, genotypically normal (46,XX) female patient shows symptoms of hypoglycemia (low blood glucose) and hypotonia (decreased muscle tone).  Physical examination reveals abnormal development of the external genitalia, and laboratory studies show elevated urinary sodium content, increased serum levels of potassium, and abnormal serum concentration of several steroid hormones.  The patient is diagnosed with 21-hydroxylase deficiency, the most common type of congenital adrenal hyperplasia (CAH).CAH refers to a group of autosomal recessive diseases, each associated with defective production of one or more steroid hormones by the adrenal glands, two crescent-shaped glands located above each kidney in the abdominal cavity.  It has been reported that unequal crossing over involving chromosome 6 can result in CAH.  More than 90% of CAH diagnoses are associated with a deficiency of 21-hydroxylase, an enzyme encoded by the CYP21A2 gene on chromosome 6.Normally, 21-hydroxylase catalyzes chemical reactions involved in the synthesis of aldosterone and cortisol, the principal mineralocorticoid and glucocorticoid hormones, respectively.  As a result, patients with 21-hydroxylase deficiency exhibit diminished serum levels of aldosterone and cortisol.  However, synthesis and secretion of the sex hormone testosterone is excessive.  Among the normal actions of glucocorticoids are metabolic and anti-inflammatory effects, and glucocorticoid deficiency disrupts the negative feedback loop linking the brain to the adrenal gland.  Glucocorticoid deficiency can lead to hyperplasia (increased cell proliferation) of adrenal tissue.The patient's 21-hydroxylase deficiency is treated with regular administration of synthetic steroid hormones.  Her condition improves after receiving these medications. Question 30Given that the fusion of male and female gametes results in fertilization, which statement best explains how unequal crossing over during gametogenesis led to 21-hydroxylase deficiency in the fertilized embryo?  One of the parental gametes:A.contained an extra copy of chromosome 6.B.contained no copies of chromosome 6.C.experienced an event in which the CYP21A2 gene was duplicated.D.underwent an event in which the CYP21A2 gene was deleted.

Treatment for CAH requires the replacement of:

Hypernatremia commonly occurs in _____Group of answer choicesDecreased production of antidiuretic hormone (ADH)Syndrome of inappropriate ADH (siADH)Decreased aldosteroneNephrotic syndrome

An increased blood calcium level stimulates the release of:Multiple choice question.calcitriolcalcitoninparathyroid hormone (PTH)

Parathyroid hormone (PTH) serves a key role in calcium homeostasis.  The main function of PTH is to increase plasma calcium concentration.  PTH secretion is closely regulated by changes in plasma calcium concentration, which are detected by the human calcium-sensing receptor (hCaSR), a G protein–coupled receptor located on chief cells of the parathyroid gland.  hCaSR activation ultimately inhibits PTH release by inducing a second messenger cascade in which intracellular calcium levels rise due to the hydrolysis of the membrane phospholipid phosphatidylinositol bisphosphate (PIP2) into inositol trisphosphate (IP3) and diacylglycerol (DAG) by the membrane-bound enzyme phospholipase C (PLC).Secondary hyperparathyroidism (SHPT) is a condition characterized by excessive PTH release in response to depressed serum calcium or elevated serum phosphate levels.  The novel peptide AMG 416, an hCaSR agonist, is being investigated as a possible treatment for SHPT caused by end-stage renal disease (ESRD).  IP-1, a metabolite that acts downstream of IP3, is a marker of hCaSR activity.  Researchers used embryonic kidney cells lacking hCaSR (HEK-293T) and HEK-293T clone cells stably transfected with hCaSR (hCaSR) to measure IP-1 levels following AMG 416 treatment (Figure 1).Figure 1  IP-1 concentration in embryonic kidney cells lacking hCaSR (HEK-293T) and HEK-293T clone cells transfected with hCaSR (hCaSR) following AMG 416 treatmentThe dependence of AMG 416 on extracellular calcium was investigated by incubating hCaSR cells with increasing concentrations of AMG 416 in the presence or absence of calcium (Figure 2).Figure 2  IP-1 levels in hCaSR cells incubated with and without calcium and AMG 416 peptide (Note: IP-1 levels are normalized to the number of cells present in each culture.)In addition, the effect of AMG 416 on PTH concentration was measured in wild-type (WT) rats.  Blood samples were taken from male and female rats for 8 hours following administration of varying concentrations of AMG 416 (Figure 3), and PTH levels were measured.Figure 3  Serum PTH concentration following administration of AMG 416 to WT ratsAMG 416 (Velcalcetide) Activates the Calcium Sensing Receptor. Sarah Walter, Amos Baruch, Jin Dong, et al. Journal of Pharmacology and Experimental Therapeutics August 1, 2013, 346 (2) 229-240 Question 39Which of the following is a potential complication of secondary hyperparathyroidism?A.Decreased bone mineralizationB.Decreased osteoclast activityC.Increased osteoblast activityD.Increased cortical bone massSubmit