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Hormones

Q.1- A dietary deficiency of iodine would do which of the following?

a) Directly affect the synthesis of Thyroglobulin

b) Result in increased secretion of Thyroid stimulating hormone (TSH)

c) Result in decreased production of Thyrotropin releasing hormone

d) Result in increased basal metabolic rate

e) Raise the blood pressure and heart rate

Q.2- Which of the following acts to increase the release of Ca ++ from the endoplasmic reticulum?

a) Diacylglycerol (DAG)

b) Inositol tri phosphate

c) Parathyroid hormone

D) Calcitonin

e) 1, 25- Dihydroxycholecalciferol (1, 25-DHC)

Q.3- Which of the following stimulates the synthesis of milk protein?

a) Luteinizing Hormone (LH)

b) Prolactin (PRL)

c) Thyroid stimulating hormone (TSH)

d) Growth hormone (GH)

e) FSH (Follicle stimulating hormone)

Q.4- The release of which of the following is inhibited by thyroxine?

a)LH

b) PRL

c) TSH

d) GH

e) FSH

Q.5- Which of the following hormones promotes hypoglycemia?

a) Epinephrine

b) Nor epinephrine

c) Insulin

d) Growth hormone

e) Glucagon

Q.6- Increased reabsorption of water from kidney is the major consequence of which of the following hormones?

a) Cortisol

b) Insulin

c) Vasopressin

d) Glucagon

e) Aldosterone

Q.7- Lack of glucocorticoids and mineralocorticoids might be a consequence of which of the following defects in the adrenal cortex?

a) Estrone deficiency

b) Testosterone deficiency

c) 17-α hydroxy progesterone deficiency

d) Androstenedione deficiency

e) C 21- hydroxylase deficiency

Q.8- Which of the following hormones can cause hyperglycemia without known effects on glycogen or gluconeogenesis?

a) Thyroxine

b) Epinephrine

c) Glucocorticoids

d) Glucagon

e) Growth hormone

Q.9 – Which of the following statements best describes Insulin?

a) Its action is antagonistic to that of Glucagon

b) It is a small peptide composed of a single chain bridged by disulfide groups

c) It does not have a prohormone form

d) It promotes glucose absorption from  intestine and renal tubular cells

e) It has a direct role in the uptake of glucose in nerve and red blood cells

Q.10- Which of the following is noted in Cushing’s syndrome, a disease of adrenal cortex?

a) Decreased production of epinephrine

b) Excessive production of vasopressin

c) Excessive production of cortisol

d) Decreased production of cortisol

e) Deceased production of Norepinephrine

Q.11- Which of the following statements best describes the mechanism of action of sex hormones?

a) They bind specific membrane receptors

b) They interact with DNA directly

c) They cause release of second messenger from the cell membrane

d) They enhance transcription when bound to receptors

e) They inhibit translation through specific cytoplasmic proteins

 Q.12- Which of the following stimulates the production of progesterone by the corpus luteum?

a) LH

b) PRL

c) TSH

d) GH

e) FSH

Q.13- Which of the following pituitary hormones will increase if communication from the hypothalamus is severed?

a) GH

b) TSH

c) PRL

d) Vasopressin

e) Cortisol

Q.14- Which of the following hormones is associated with diuresis?

a) Oxytocin

b) Vasopressin

c) Prolactin

d) Estrogen

e) None of the above

Q.15- A 73-year-old woman is transferred to intensive care unit after she is found to be in septic shock. It is believed that she originally had a urinary tract infection and that the bacteria seeded her blood stream. The critical care fellow is concerned she may not have an adequate stress response in this situation. He orders a cosyntropin test, which evaluates the body’s ability to produce which of the following hormones?

a) Oxytocin

b) Vasopressin

c) Cortisol

d) Corticotropin releasing hormone

e) Adrenocorticotropic hormone (ACTH)

Q.16. – Which of the following hormones is secreted in response to Angiotensin II?

a) Cortisol

b) Aldosterone

c) Thyroxin

d) Estrogen

e) FSH

Q.17- A 23-year-old woman has been referred from an endocrinologist for weight gain especially around the waist. She also has striae over the abdomen and a rounded appearance to her face. She is found to have Cushing disease. Which of the following is found in this patient?

a) Deceased absorption of glucose from intestine

b) Decreased lipolysis

c) Increased protein synthesis

d) Increased gluconeogenesis

e) Decreased liver glycogen stores

Q.18-A 34-year-old man comes to the emergency room with a headache and a blurred vision. He complains that his wedding ring no longer fits him and that his favorite hat no longer fits on his head. His wife feels that his nose has become wider. He is found to have Acromegaly. Which of the following metabolic effects would you expect in this patient?

a) Decreased protein synthesis

b) Inhibition of gluconeogenesis

c) Inhibition of lipolysis

d) Increased protein synthesis

e) Increased cholesterol synthesis

Q.19- A 75-year-old woman with osteoporosis complains of back pain. A magnetic resonance imaging (MRI) scan of her back confirms a compressing fracture of the L3 vertebra. The attending physician begins treating the patient with morphine for pain control. Morphine is an analgesic that works similarly to which of the following endogenously produced substance?

a) ACTH

b) POMC

c) MSH

d) Endorphin

e) Lipotropin

 Q.20- A 56-year- old woman with a 60-pack year history of smoking is recently found to have a large mass in her lungs, likely a tumor. Her basic lab demonstrates a reduce serum sodium of 127 mmol/L and a reduced urine osmolality. She likely has which of the following endocrine abnormalities?

a) Cushing disease

b) Syndrome of inappropriate secretion of ADH (SIADH)

c) Cushing syndrome

d) Acromegaly

e) Prolactinoma

Q.21- A 75-year-old man complains of increased urinary frequency, especially at night. he has difficulty starting to urinate and often dribbles urine when he finishes. His urologist suspects benign hyperplasia and places him on a 5-α-Reductase inhibitor. This would decrease which of the following?

a) Conversion of c-AMP to adenosine

b) Release of calcium from endoplasmic reticulum

c) Prostaglandin synthesis

d) Conversion of Angiotensin I to Angiotensin II

e) Conversion of testosterone to dihydrotestosterone (DHT)

Key to answers

1)- b, 2)-b, 3)-b, 4)-C, 5)-c, 6)-c, 7)-e,8)-a, 9)-a, 10)-c,11)-d,12)-a, 13)-c, 14)-e,15)-c, 16)-b, 17)-d, 18)-d, 19)-d, 20)-b, 21)-e

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Case details

 A 23-year-old male was seen in the emergency department after suffering a concussion and head trauma from a motor vehicle accident. The patient was stabilized in the emergency department and transferred to the intensive care unit (ICU) for observation. The patient had computed tomography(CT) scan of the head that revealed a small amount of cerebral edema but was otherwise normal. During the second day in the ICU, the nurse informed that the patient had a large amount of urine output in the last 24 hours. The nursing records reported his urine output over the previous 24 hours to be 5000 cc. He had not been given any diuretic medications. A urine osmolality was ordered and was found to be low. His physician remarked that the kidneys were not concentrating urine normally.

What is the most likely diagnosis for the increasing dilute urine output?

Which biochemical mediator is responsible for this disorder ?

Case discussion-  The patient is suffering from Diabetes Insipidus.  Excessive excretion of diluted urine with a low osmolarity and history of head injury are all suggestive of diabetes Insipidus. Head trauma is one of the most common causes of diabetes Insipidus, particularly if the posterior pituitary stalk is disrupted. 

Polyuria, Polydipsia, high plasma osmolarity and a low urinary osmolarity are hall marks of diabetes Insipidus. Diabetes Insipidus is not the same as diabetes mellitus (“sugar” diabetes).  Diabetes Insipidus resembles diabetes mellitus because the symptoms of both diseases are increased urination and thirst.  However, in every other respect, including the causes and treatment of the disorders, the diseases are completely unrelated.   Sometimes diabetes Insipidus is referred to as “water” diabetes to distinguish it from the more common diabetes mellitus or “sugar” diabetes.

 Pathophysiology           

The regulation of urine production occur in the hypothalamus, which produces ADH in the supraoptic and Para ventricular nuclei. After synthesis, the hormone is transported in neuro secretory granules down the axon of the hypothalamic neuron to the posterior lobe of the pituitary gland where it is stored for later release ( figure-1).

 Release of ADH

Figure-1- Synthesis, storage and release of ADH

 In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex (figure-2).

Osmotic regulation by ADH

Figure-2- Excessive water intake leads to dilutional effect with the resultant decease in plasma osmolality that leads to decreased release of ADH. There is less water  reabsorption and diuresis is promoted. Reverse occurs with a decreased intake of water, a concentrated urine  is excreted due to more water reabsorption under the effect of ADH.

The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubule, specifically it acts on proteins called aquaporins which open to allow water into the collecting duct cells(figure-3).This increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.

Water reabsorption mediated by ADH

Figure-3- Under the effect of ADH aquaporins open up to allow reabsorption of water, a concentrated urine is excreted. Reverse occurs in the absence of ADH.

Signs and symptoms

  • Excessive urination and extreme thirst are typical for DI. Symptoms of diabetes Insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine does not contain glucose and there is no hyperglycemia.
  • Signs of dehydration may also appear in some individuals since the body cannot conserve much of the water it takes in.
  • The extreme urination continues throughout the day and the night.
  • In children, DI can interfere with appetite, eating, weight gain, and growth as well.
  • They may present with fever, vomiting, or diarrhea.
  • Adults with untreated DI may remain healthy for decades as long as enough water is consumed to offset the urinary losses. However, there is a continuous risk of dehydration and loss of potassium.

Biochemical defect –Diabetes Insipidus is divided into four types, each of which has a different cause and must be treated differently. 

1) Central or neurogenic DI- The most common type of DI is caused by a lack of vasopressin, a hormone that normally acts upon the kidney to reduce urine output by increasing the concentration of the urine.  This type of DI is usually due to the destruction of the “posterior” part of the pituitary gland where vasopressin is normally produced.  Hence, it is commonly called pituitary DI.   

The posterior pituitary can be destroyed by a variety of underlying diseases including tumors, infections, head injuries (as in the given patient), infiltrations, and various inheritable defects. The later can be recognized by the onset of the DI in early childhood and a family history of parents, siblings or other relatives with the same disorder.  Nearly half the time, however, pituitary DI is” idiopathic” (that is, no cause can be found despite a thorough search including magnetic resonance imaging or MRI of the brain) and the underlying cause(s) is (are) still unknown.  

2) Gestagenic or gestational DI –Occasionally, a lack of vasopressin can also develop during pregnancy if the pituitary is slightly damaged and/or the placenta destroys the hormone too rapidly. 

3) Nephrogenic DI -The third type of DI is caused by an inability of the kidneys to respond to the “antidiuretic effect” of normal amounts of vasopressin.  The kidneys’ ability to respond to ADH can be impaired by drugs—like lithium, for example—and by chronic disorders including polycystic kidney disease, sickle-cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders.

4) Dipsogenic DI –The fourth form of DI occurs when vasopressin is suppressed by excessive   intake of fluids.  The latter is usually referred to as primary polydipsia and is most often caused by an abnormality in the part of the brain that regulates thirst.  This subtype is difficult to differentiate from pituitary DI particularly since the two disorders can result from  many of the same brain diseases. 

Diagnosis

Diagnosis is based on a series of tests, including urinalysis and a fluid deprivation test.

Urine analysis –The urine of a person with DI will be less concentrated.
A fluid deprivation test helps determine whether DI is caused by one of the following:

  • excessive intake of fluid
  • a defect in ADH production
  • a defect in the kidneys’ response to ADH

This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary.

Desmopressin stimulation Test –To distinguish between the main forms,desmopressin stimulation is also used; desmopressin can be taken by injection,a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.
In order to distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops).
In some patients, a magnetic resonance imaging (MRI) of the brain may be necessary as well.

Treatment

Central DI and gestational DI respond to desmopressin, a synthetic analogue of ADH. Gestational DI tends to abate on it sown 4 to 6 weeks following labor, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option. Desmopressin is ineffective in nephrogenic DI. 
Again, adequate hydration is important for patients with DI, as they may become dehydrated easily.

 

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Case Details

A 22- year-old diabetic comes to the Accident and Emergency department. She gives a 2-day history of vomiting and abdominal pain. She is drowsy and her breathing is deep and rapid. There is distinctive smell from her breath

What is the most likely diagnosis?

What is the biochemical basis for all the presenting symptoms?
Which laboratory test would you request?
Case discussion The patient is most probably suffering from diabetic ketoacidosis. She is a known diabetic and the presenting symptoms like abdominal pain, vomiting, rapid breathing and distinctive smell of breath, all indicate associated ketoacidosis.
Basic concept Diabetic Ketoacidosis (DKA) is a state of inadequate insulin levels resulting in high blood sugar and accumulation of organic acids and ketones in the blood.  It is a potentially life-threatening complication in patients with diabetes mellitus. It happens predominantly in type 1 diabetes mellitus, but it can also occur in type 2 diabetes mellitus under certain circumstances.

Causes- DKA occurs most frequently in knownDiabetics. It may also be the first presentation in patients who had not been previously diagnosed as diabetics. There is often a particular underlying problem that has led to DKA episode. This may be-

1) Inter current illness such as Pneumonia,Influenza, Gastroenteritis, Urinary tract infection or pregnancy.

2) Inadequate Insulin administration may be due to defective insulin pen device or in young patient intentional missing of dose due to fear of weight gain.

3) Associated myocardial infarction, stroke or use of cocaine

4) Inadequate food intake– may be due to anorexia associated with infective process or due to eating disorder in children. 

Diabetic keto acidosis may occur in those previously known to have diabetes mellitus type 2 or in those who on further investigations turn out to have features of type 2 diabetes (e.g. obesity,strong family history); this is more common in African, African-American and Hispanic people. Their condition is then labelled “ketosis-prone type 2 diabetes”.

Pathophysiology

DKA results from relative or absolute insulin deficiency combined with counter regulatory hormone excess (Glucagon, Catecholamines, cortisol, and growth hormone). The decreased ratio of insulin to Glucagon promotes Gluconeogenesis,glycogenolysis, and Ketone body formation in the liver, as well as increases in substrate delivery from fat and muscle (free fatty acids, amino acids) to the liver. 

a) Cause of hyperglycemia Uncontrolled IDDM leads to increased hepatic glucose output.First, liver glycogen stores are mobilized then hepatic gluconeogenesis is used to produce glucose. Insulin deficiency also impairs non-hepatic tissue utilization of glucose. In particular in adipose tissue and skeletal muscle,insulin stimulates glucose uptake. This is accomplished by insulin-mediated movement of glucose transporter proteins to the plasma membrane of these tissues.

Reduced glucose uptake by peripheral tissues in turn leads to a reduced rate of glucose metabolism. In addition, the level of hepatic Glucokinase is regulated by insulin. Therefore, a reduced rate of glucose phosphorylation in hepatocytes leads to increased delivery to the blood. Other enzymes involved in anabolic metabolism of glucose are affected by insulin(primarily through covalent modifications). The combination of increased hepatic glucose production and reduced peripheral tissues metabolism leads to elevated plasma glucose levels.

b) Cause of kenosis One major role of insulin is to stimulate the storage of food energy following the consumption of a meal. This energy storage is in the form of glycogen in hepatocytes and skeletal muscle. Additionally, insulin stimulates hepatocytes to synthesize triglycerides and storage of triglycerides in adipose tissue. In opposition to increased adipose storage of triglycerides is insulin-mediated inhibition of lipolysis. In uncontrolled IDDM there is a rapid mobilization of triglycerides leading to increased levels of plasma free fatty acids. 

The free fatty acids are taken up by numerous tissues (however, not the brain) and metabolized to provide energy.Free fatty acids are also taken up by the liver. Normally, the levels of malonyl-CoA are high in the presence of insulin. These high levels of malonyl-CoA inhibit carnitine palmitoyl Transferase I, the enzyme required for the transport of fatty acyl-CoA’s into the mitochondria where they are subject to oxidation for energy production.

Thus, in the absence of insulin,malonyl-CoA levels fall and transport of fatty acyl-CoA’s into the mitochondria increases. Mitochondrial oxidation of fatty acids generates acetyl-CoA which can be further oxidized in the TCA cycle. However, in hepatocytes the majorityof the acetyl-CoA is not oxidized by the TCA cycle but is metabolized into the ketone bodies, Acetoacetate and β-hydroxybutyrate.  TCA cycle is in a state of suppression due to non availability of oxaloacetate which is channeled towards pathway of gluconeogenesis in the absence of Insulin. 

These ketone bodies leave the liver and are used for energy production by the brain, heart and skeletal muscle. In IDDM, the increased availability of free fatty acids and ketone bodies exacerbates the reduced utilization of glucose furthering the ensuing hyperglycemia. Production of ketone bodies, in excess of the body’s ability to utilize them leads to ketoacidosis. In diabetics, this can be easily diagnosed by smelling the breath. A spontaneous breakdown product of Acetoacetate is acetone which is volatilized by the lungs producing a distinctive odor.

c) Causes of Acidosis and hyperventilationThe ketone bodies, however, have a low pH and therefore turn the blood acidic(metabolic acidosis). The body initially buffers this with the bicarbonate buffering system, but this is quickly overwhelmed and other mechanisms to compensate for the acidosis, such as hyperventilation to lower the blood carbon dioxide levels. This hyperventilation, in its extreme form, may be observed as Kussmaul respiration. Ketones, too,participate in osmotic diuresis and lead to further electrolyte losses. As a result of the above mechanisms, the average adult DKA patient has a total body water shortage of about 6 liters (or 100 ml/kg), in addition to substantial shortages in sodium, potassium, chloride, phosphate, magnesium and calcium. Glucose levels usually exceed 13.8 mmol/l or 250 mg/dl. 

Increased lactic acid production also contributes to the acidosis. The increased free fatty acids increase triglyceride and VLDL production. VLDL clearance is also reduced because the activity of insulin-sensitive lipoprotein lipase in muscle and fat is decreased. Most commonly, DKA is precipitated by increased insulin requirements, as might occur during a concurrent illness. Occasionally, complete omission of insulin by the patient with type 1 DM precipitates DKA.

Clinical manifestations– The symptoms of an episode of diabetic ketoacidosis usually evolve over the period of about 24 hours. Predominant symptoms are nausea and vomiting, pronounced thirst,excessive urine production and abdominal pain that may be severe.

Hyperglycemia is always present .In severe DKA, breathing becomes labored and of a deep, gasping character (a state referred to as “Kussmaul respiration”). The abdomen may be tender to the point that an acute abdomen may be suspected, such as acute pancreatitis, appendicitis or gastrointestinal perforation.  

Coffee ground vomiting(vomiting of altered blood) occurs in a minority of patients; this tends to originate from erosions of the esophagus. In severe DKA, there may be confusion, lethargy, stupor or even coma(a marked decrease in the level of consciousness).

On physical examination -there is usually clinical evidence of dehydration, such as a dry mouth and decreased skin turgor. If the dehydration is profound enough to cause a decrease in the circulating blood volume, tachycardia (a fast heart rate) and low blood pressure may be observed. Often, a “ketotic”odor is present, which is often described as “fruity”. If Kussmaul respiration is present, this is reflected in an increased respiratory rate.

Small children with DKA are relatively prone to cerebral edema (swelling of the brain tissue), which may cause headache, coma, loss of the pupillary light reflex, and progress to death. It occurs in 0.7–1.0% of children with DKA, and has been described in young adults, but is  very rare in adults. It carries 20–50% mortality. 

 

Figure- showing causes and consequences of DKA

Diagnosis

Investigations-  Diabetic Ketoacidosis may be diagnosed when the combination of hyperglycemia (high blood sugars), ketones on urinalysis and acidosis are demonstrated.

Arterial blood gas measurement is usually performed to demonstrate the acidosis; this requires taking a blood sample from an artery.

In addition to the above, blood samples are usually taken to measure urea and creatinine (measures of kidney function, which may be impaired in DKA as a result of dehydration) and electrolytes.

Furthermore, markers of infection (complete blood count, C-reactive protein) and acute pancreatitis (amylase and lipase) may be measured.

Given the need to exclude infection, chest radiography and urinalysis are usually performed.If cerebral edema is suspected because of confusion, recurrent vomiting or other symptoms, computed tomography may be performed to assess its severity and to exclude other causes such as stroke.

Management

 The main aims in the treatment of diabetic ketoacidosis are replacing the lost fluids and electrolytes while suppressing the high blood sugars and ketone production with insulin.

a) Fluid replacement The amount of fluid depends on the estimated degree of dehydration. If dehydration is sosevere, rapid infusion of saline is recommended to restore circulating volume.

 b) Insulin is usually given continuously.

c) Potassium levels can fluctuate severely during the treatment of DKA, because insulin decreases potassium levels in the blood by redistributing it into cells. Serum potassium levels are initially often mildly raised even though total body potassium is depleted. Hypokalemia often follows treatment. This increases the risk of irregularities in the heart rate. Therefore, continuous observation of the heart rate is recommended, as well as repeated measurement of the potassium levels and addition of potassium to the intravenous fluids once levels fall below 5.3 mmol/l. If potassium levels fall below 3.3 mmol/l, insulin administration may need to be interrupted to allow correction of the hypokalemia.

d) Bicarbonate- Sodium bicarbonate solution is administered to rapidly improve the acid levels in the blood.

Cerebral edema- administration of fluids is slowed; intravenous Mannitol and hypertonic saline (3%) are used.

Prognosis

With appropriate therapy, the mortality of DKA is low (<5%) and is related more to the underlying or precipitating event, such as infection or myocardial infarction. The major non metabolic complication of DKA therapy is cerebral edema,which most often develops in children as DKA is resolving.

The etiology of and optimal therapy for cerebral edema are not well established, but over replacement of free water should be avoided. The other known complications of DKA therapy are, Hypoglycemia, hypokalemia and hypophosphatemia. Venous thrombosis, upper gastrointestinal bleeding, and acute respiratory distress syndrome occasionally complicate DKA.

Prevention of DKA

Following treatment, the physician and patient should review the sequence of events that led to DKA to prevent future recurrences. Foremost is patient education about the symptoms of DKA, its precipitating factors, and the management of diabetes during a concurrent illness.

During illness or when oral intake is compromised, patients should:

(1) frequently measure the capillary blood glucose;

(2) measure urinary ketones when the serum glucose > 16.5 mmol/L (300 mg/dL);

(3) drink fluids to maintain hydration;

(4) continue or increase insulin; and

(5) seek medical attention if dehydration, persistent vomiting, or uncontrolled hyperglycemia develop. Using these strategies, early DKA can be prevented or detected and treated appropriately on an outpatient basis.

DKA IN PREGNANCY-   DKA in pregnancy is of special concern. It tends to occur at lower plasma glucose levels and more rapidly than in non-pregnant patients and usually occurs in the second and third trimesters because of increasing insulin resistance. Fetal mortality rates have previously been reported as high as 30% rising to over 60% in DKA with coma. However with improvements in diabetic care the figure for fetal loss has been reported as low as 9% in some countries. Prevention, early recognition and aggressive management are vitally important to minimize fetal mortality.

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Case Details

A 35 year -old female reported to emergency with severe pain in the left flank region, which was radiating towards lower leg and back. The patient was in acute distress and agony. History revealed that she frequently suffered from urinary tract infections and had several such episodes of pain. She further reported that she constantly felt weakness, fatigue and bone pains from the previous few months.

There was no history of fever and there was no personal or family history of medical problems.

Her physical examination was normal except for tenderness in the left renal region.The attending physician ordered for complete blood count, electrolytes and a complete urinalysis.

The laboratory investigation report revealed a normal complete blood count (CBC), and significantly elevated calcium level and low phosphorus level.Urine was cloudy and had plenty of pus cells. The patient was admitted and treated for renal colic.

What is the underlying cause for repeated episodes of renal colic?

What is the most likely diagnosis?

What is the relationship of bone pains and frequent urinary tract infections in this patient?

What is the cause for high serum calcium and low phosphorus level in this patient?

 

Case details Hypercalcemia, hypophosphatemia, recurrent urinary tract infections, renal stones and bone pains all signify underlying hyperparathyroidism. (Cloudy urine and pus cells are indicative of urinary tract infection).

Hyperparathyroidism is over activity of the parathyroid glands resulting in excess production of parathyroid hormone (PTH). The parathyroid hormone regulates calcium and phosphate levels.  

Hyperparathyroidism is classified in three categories-

1) Primary hyperparathyroidism-Primary hyperparathyroidism results from a hyper function of the parathyroid glands themselves. There is over secretion of PTH due to adenoma, hyperplasia or,rarely, carcinoma of the parathyroid glands.

2) Secondary hyperparathyroidism-Secondary hyperparathyroidism is the reaction of the parathyroid glands to a hypocalcaemia caused by something other than a parathyroid pathology, e.g.chronic renal failure or vitamin D deficiency.

3)Tertiary hyperparathyroidism- Tertiary hyperparathyroidism results from hyperplasia of the parathyroid glands and a loss of response to serum calcium levels. In cases of long-standing secondary hyperparathyroidism, the hypertrophied parathyroid glands can become autonomously functioning and continue to secrete PTH independent of whether the original stimuli to secrete PTH are still present.

In all cases, the raised PTH levels are harmful to bone, and treatment is often needed.

Serum calcium- In cases of primary hyperparathyroidism or tertiary hyperparathyroidism heightened PTH leads to increased serum calcium (Hypercalcemia) due to:

  1. increased bone resorption, allowing flow of calcium from bone to blood
  2. reduced renal clearance of calcium
  3. increased intestinal calcium absorption

By contrast, in secondary hyperparathyroidism effectiveness of PTH is reduced.

Serum phosphate

In primary hyperparathyroidism, serum phosphate levels are abnormally low as a result of decreased renal tubular phosphate reabsorption. However, this is only present in about 50% of cases.This contrasts with secondary hyperparathyroidism, in which serum phosphate levels are generally elevated because of renal disease.

Manifestations of hyperparathyroidism involve primarily the kidneys and the skeletal system. Kidney involvement is due to either deposition of calcium in the renal parenchyma or to recurrent nephrolithiasis. Renal stones are usually composed of either calcium oxalate or calcium phosphate. In occasional patients,repeated episodes of nephrolithiasis or the formation of large calculi may lead to urinary tract obstruction, infection, and loss of renal function. 

Nephrocalcinosis may also cause decreased renal function and phosphate retention.

There are great variations in the manifestations. Patients may present with multiple signs and symptoms, including recurrent nephrolithiasis, peptic ulcers,mental changes, and, less frequently, extensive bone resorption.

Treatment and monitoring Treatment depends upon the severity and cause of the condition. If there is mildly increased calcium levels due to primary hyperparathyroidism and no symptoms, just regular check ups are needed. If symptoms are present or calcium level is very high, surgery may be needed to remove the parathyroid gland that is overproducing the hormone. Treatment of secondary hyperparathyroidism depends on the underlying cause.Vitamin D and Phosphorus supplementation can also be done. 

Calcimimetics

A Calcimimetics (cinacalcet) is a new type of drug for people with primary and secondary hyperparathyroidism on dialysis. It mimics the effect of calcium in tissues. This reduces PTH release from parathyroid glands, leading to lower calcium and phosphorus levels in blood. 

Surgery for hyperparathyroidism may lead to low blood calcium levels, which causes tingling and muscle twitching. This requires immediate treatment.

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Case Details

A 35 year -oid female reported to emergency with severe pain in the left flank region, which was radiating towards lower leg and back. The patient was in acute distress and agony. History revealed that she frequently suffered from urinary tract infections and had several such episodes of pain.She further reported that she constantly felt weakness, fatigue and bone pains from the previous few months. There was no history of fever and there was no personal or family history of medical problems.

Her physical examination was normal except for tenderness in the left renal region.

The attending physician ordered for complete blood count, electrolytes and a complete urinalysis.

The laboratory investigation report revealed a normal complete blood count (CBC), and significantly elevated calcium level and low phosphorus level. Urine was cloudy and had plenty of pus cells. The patient was admitted and treated for renal colic.

What is the underlying cause for repeated episodes of renal colic?

What is the most likely diagnosis?

What is the relationship of bone pains and frequent urinary tract infections in this patient?

What is the cause for high serum calcium and low phosphorus level in this patient?


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A 23-year-old male was seen in the emergency department after suffering a concussion and head trauma from a motor vehicle accident. The patient was stabilized in the emergency department and transferred to the intensive care unit (ICU) for observation. The patient had computed tomography(CT) scan of the head that revealed a small amount of cerebral edema but was otherwise normal. During the second day in the ICU, the nurse informed that the patient had a large amount of urine output in the last 24 hours. The nursing records reported his urine output over the previous 24 hours to be 5000 cc. He had not been given any diuretic medications. A urine osmolality was ordered and was found to be low. His physician remarked that the kidneys were not concentrating urine normally.

What is the most likely diagnosis for the increasing dilute urine output?

Which biochemical mediator is responsible for this disorder ?

Case details The patient is suffering from Diabetes Insipidus.  Excessive excretion of diluted urine with a low osmolarity and history of head injury are all suggestive of diabetes Insipidus. Head trauma is one of the most common causes of diabetes Insipidus, particularly if the posterior pituitary stalk is disrupted. 

Polyuria, Polydipsia,high plasma osmolarity and a low urinary osmolarity are hall marks of diabetes Insipidus. Diabetes Insipidus is not the same as diabetes mellitus (“sugar” diabetes).  Diabetes Insipidus resembles diabetes mellitus because the symptoms of both diseases are increased urination and thirst.  However, in every other respect, including the causes and treatment of the disorders, the diseases are completely unrelated.   Sometimes diabetes Insipidus is referred to as”water” diabetes to distinguish it from the more common diabetes mellitus or “sugar” diabetes.

 

Pathophysiology           

The regulation of urine production occur in the hypothalamus, which produces ADH in the supraoptic and Para ventricularnuclei. After synthesis, the hormone is transported in neuro secretory granules down the axon of the hypothalamic neuron to the posterior lobe of the pituitargland where it is stored for later release. In addition, the hypothalamus regulates the sensation of thirst in the ventromedial nucleus by sensing increases in serum osmolarity and relaying this information to the cortex.

The main effector organ for fluid homeostasis is the kidney. ADH acts by increasing water permeability in the collecting ducts and distal convoluted tubule, specifically it acts on proteinscalled aquaporins which open to allow water into the collecting duct cells.This increase in permeability allows for reabsorption of water into the bloodstream, thus concentrating the urine.

Signs and symptoms

Excessive urination and extreme thirst are typical for DI. Symptoms of diabetes Insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine does not contain glucose and there is no hyperglycemia. Signs of dehydration may also appear in some individuals since the body cannot conserve much of the water it takes in.

The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating,weight gain, and growth as well. They may present with fever, vomiting, ordiarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is consumed to off set the urinary losses. However, there is a continuous risk of dehydration and loss of potassium.

Biochemical defect –Diabetes Insipidus is divided into four types, each of which has a different cause and must be treated differently. 

1) Central or neurogenic DI- The most common type of DI is caused by a lack of vasopressin, a hormone that normally acts upon the kidney to reduce urine output by increasing the concentration of the urine.  This type of DI isusually due to the destruction of the “posterior” part of the pituitary gland where vasopressin is normally produced.  Hence, it is commonly called pituitaryDI.   

The posterior pituitary can be destroyed by a variety of underlying diseases including tumors, infections, head injuries(As in the given patient), infiltrations, and various inheritable defects. The latter can be recognized by the onset of the DI in early childhood and a family history of parents, siblings or other relatives with the same disorder.  Nearly half the time, however, pituitary DI is”idiopathic” (that is, no cause can be found despite a thorough search including magnetic resonance imaging or MRI of the brain) and the underlying cause(s) is (are) still unknown.  

2) Gestagenic or gestational DI –Occasionally,a lack of vasopressin can also develop during pregnancy if the pituitary is slightly damaged and/or the placenta destroys the hormone too rapidly. 

3) Nephrogenic DI -The third type of DI is caused by an inability of the kidneys to respond to the “antidiuretic effect” of normal amounts of vasopressin.  The kidneys’ ability to respond to ADH can be impaired bydrugs—like lithium, for example—and by chronic disorders including polycystic kidney disease, sickle-cell disease, kidney failure, partial blockage of the ureters, and inherited genetic disorders.

4) DipsogenicDI –The fourth form of DI occurs when vasopressin is suppressed by excessive intake of fluids.  The latter is usually referred to as primary polydipsia and is most often caused by an abnormality in the part of the brain that regulates thirst.  This subtype is difficult to differentiate from pituitary DI particularly since the two disorders can result form  many of the same brain diseases. 

Diagnosis

Diagnosis is based on a series of tests,including urinalysis and a fluid deprivation test.

Urine analysis –The urine of a person with DI will be less concentrated.
A fluid deprivation test helps determine whether DI is caused by one of the following:

 

  • excessive intake of fluid
  • a defect in ADH production
  • a defect in the kidneys’ response to ADH

This test measures changes in body weight,urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary.

Desmopressin stimulation Test –To distinguish between the main forms,desmopressin stimulation is also used; desmopressin can be taken by injection,a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in the central nervous system. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.
In order to distinguish DI from other causes of excess urination, blood glucose levels, bicarbonate levels, and calcium levels need to be tested. Measurement of blood electrolytes can reveal a high sodium level (hypernatremia as dehydration develops).
In some patients, a magnetic resonance imaging (MRI) of the brain may be necessary as well.

Treatment

Central DI and gestational DI respond todesmopressin, a synthetic analogue of ADH. Gestational DI tends to abate on itsown 4 to 6 weeks following labor, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is not usually an option.

Desmopressin is ineffective in nephrogenic DI. 
Again, adequate hydration is important for patients with DI, as they may become dehydrated easily.


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Case Details

A 23-year-old male was seen in the emergency department after suffering a concussion and head trauma from a motor vehicle accident. The patient was stabilized in the emergency department and transferred to the intensive care unit (ICU) for observation. The patient had computed tomography(CT) scan of the head that revealed a small amount of cerebral edema but was otherwise normal.

During the second day in the ICU, the nurse informed that the patient had a large amount of urine output in the last 24 hours. The nursing records reported his urine output over the previous 24 hours to be 5000 cc. He had not been given any diuretic medications. A urine osmolality was ordered and was found to be low. His physician remarked that the kidneys were not concentrating urine normally.

What is the most likely diagnosis for the increasing dilute urine output?

Which biochemical mediator is responsible for this disorder ?

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