Question 1

A 45-year-old woman was being regularly reviewed in primary and secondary care because of a 5-year history of type 2 diabetes that had required early insulin treatment, refractory hypertension, and subsequent chronic kidney disease. She had previously described other symptoms, including weight gain, bruising, flushes, and low mood, all of which had been attributed to obesity and menopause. She was not taking any glucocorticoids. After presenting to her local emergency department with a Colles' fracture after a low impact fall, she was referred to the endocrinology department for suspected Cushing syndrome. Analysis for which of the following would be most useful in confirming the initial diagnosis?

Accepted Answer

Increased levels of plasma ACTH would be useful in confirming Cushing syndrome, as it indicates ACTH-dependent Cushing's, which is often due to a pituitary adenoma (Cushing's disease) or ectopic ACTH production.

Question 2

A 27-year-old woman presented to the ER complaining of nausea and vomiting for 1 week. She also reported 8 months of progressively worsening fatigue. The patient was previously very active as a ballet student, but for the past 8 months she stopped participating in ballet because of lack of energy and poor concentration. One week prior to admission, she developed nausea and had several episodes of vomiting which provoked her visit to the ER. She also reported a poor appetite for months and had lost 10 lb. Physical examination showed dryness and darkening of the skin in several areas. She repeatedly denied purposefully restricting food intake or binging and purging behaviors. There was no abdominal pain, diarrhea, fevers, dysuria, or headache. As the attending physician you suspect this patient is exhibiting signs of Addison disease. Testing for which of the following would be most useful in your diagnosis?

Accepted Answer

Decreased urinary cortisol would be useful in diagnosing Addison's disease, as it indicates adrenal insufficiency. Addison's disease is characterized by low cortisol production.  Addison disease is characterized by general malaise and debility, irritability of the stomach, and hyperpigmentation. The disease results from a primary failure of the adrenal cortex to synthesize and secrete glucocorticoid (cortisol) and mineralocorticoid (aldosterone) hormones. Currently, 70% to 90% of cases of Addison disease are the result of autoimmune adrenalitis and frequently manifests in patients with other immunological and autoimmune disorders. Addison disease frequency is higher in females than males and is usually diagnosed between 30 and 50 years of age.

Question 3

A 45-year-old woman is being examined by her physician because she is concerned about her weight gain, fatigue, muscle weakness, and thinning hair. Physical examination shows a "buffalo hump," facial hirsutism, and red striae in abdominal and underarm areas. She indicates that she is not on any medication and there is no significant past history or family history. Laboratory studies show an elevated fasting blood glucose (11 mmol/L: 198 mg/dL) and a 24-hour urinary cortisol of 2276 nmol/24 h. These signs and symptoms are most likely the result of which of the following?

Accepted Answer

The symptoms and laboratory findings are indicative of Cushing syndrome, which is characterized by excessive cortisol production leading to weight gain, muscle weakness, thinning hair, "buffalo hump," facial hirsutism, red striae, and elevated blood glucose levels.  Cushing syndrome describes the clinical consequences of chronic exposure to excess glucocorticoid irrespective of the underlying cause. Cushing syndrome may mimic common conditions such as obesity, poorly controlled diabetes, and hypertension, which progress over time and often coexist in patients with metabolic syndrome. The characteristic features of Cushing syndrome are psychiatric disturbances (depression, mania, and psychoses), central obesity, hypertension, diabetes, moon-shaped face, thin fragile skin, easy bruising, and purple striae (stretch marks). In addition, Cushing syndrome patients manifest with gonadal dysfunction that is characteristic of hyperandrogenism with excess body and facial hair (hirsutism) and acne. The most common symptoms that lead to a diagnosis of Cushing syndrome are weight gain, depression, subjective muscle weakness, and headache.

Question 4

A 63-year-old woman presented with increasing darkening of the skin, dizziness, easy fatigability, nausea with occasional vomiting, and progressive weight loss over 8 months prior to presentation. Physical examination showed a pulse of 106 bpm, supine blood pressure was 100/60 mm Hg and 70/40 mm Hg on sitting. She could not stand on account of severe postural dizziness. Radiological diagnostic tests included an abdominal ultrasound showing normal liver, spleen, pancreas, and pelvic organs. However, the left kidney was not outlined. A CT scan of the abdomen showed a nonenhancing oval-shaped left suprarenal mass with calcification. The signs and symptom in this patient are most likely the result of which of the following?

Accepted Answer

The symptoms and CT findings are consistent with Addison's disease, which is caused by adrenal insufficiency. The nonenhancing mass with calcification in the left adrenal gland suggests adrenal damage or destruction, leading to the symptoms of skin darkening, dizziness, fatigue, nausea, and hypotension.  Addison disease is characterized by general malaise and debility, irritability of the stomach, and hyperpigmentation. The disease results from a primary failure of the adrenal cortex to synthesize and secrete glucocorticoid (cortisol) and mineralocorticoid (aldosterone) hormones. One of the most common causes of Addison disease is an adrenocortical adenoma which in this case is evident from the CT scan showing a suprarenal mass.

Question 5

Which of the following processes is induced in males in response to the synthesis and release of follicle-stimulating hormone (FSH)?

Accepted Answer

FSH in males stimulates the Sertoli cells in the testes, which in turn support and promote spermatogenesis, the process of sperm production. FSH promotes testicular growth and spermatogenesis. Within the Sertoli cells of the testes it enhances the synthesis and secretion of the steroid hormones, testosterone and dihydrotestosterone.

Question 6

Congenital adrenal hyperplasia, resulting from 21-hydroxylase (CYP21A2) deficiencies, is divided into 3 distinct clinical forms. The most severe enzyme-impairing mutations result in the saltlosing form. Females with this form of the disease present at birth due to ambiguity in the external genitalia. The physiological effect of salt losing is due to which of the following hormone defects?

Accepted Answer

The salt-losing form of congenital adrenal hyperplasia is due to a deficiency in cortisol production, leading to increased ACTH release from the pituitary. This results in inadequate aldosterone production, causing salt loss.  The biological role of ACTH is to stimulate the production of adrenal cortex steroids, principally the glucocorticoids cortisol and corticosterone. ACTH also stimulates the adrenal cortex to produce the mineralocorticoid, aldosterone as well as the androgen, and androstenedione. Negative feedback on ACTH secretion is exerted by cortisol at both the hypothalamic and anterior pituitary levels. Loss of cortisol production results in unregulated and excess secretion of ACTH leading to increased androgen production resulting in the masculinizing effect seen in 21- hydroxylase deficiency.

Question 7

Which of the following is true with respect to the actions of the mineralocorticoids?

Accepted Answer

Mineralocorticoids, such as aldosterone, primarily regulate sodium retention by the kidneys, which in turn affects fluid balance and blood pressure.  The principal mineralocorticoid, produced by zona glomerulosa cells of the adrenals, is aldosterone. Synthesis of aldosterone is primarily controlled by the rennin-angiotensin system and is thus involved in control of blood pressure. Aldosterone causes sodium reabsorption by the kidneys which in turn regulates water balance and leads to increases in blood pressure by increasing fluid volume.

Question 8

A 32-year-old woman is diagnosed with hypertension, hypernatremia, hypokalemia, and alkalosis. Measurements of plasma glucocorticoid levels show them to be within the normal range; however, renin and angiotensin II levels are suppressed. Ultrasound indicates the possible existence of an adrenal cortical mass. These symptoms are likely due to excess production of which of the following hormones?

Accepted Answer

The symptoms and findings are consistent with primary hyperaldosteronism (Conn's syndrome), which is characterized by excess production of aldosterone, leading to hypertension, hypernatremia, hypokalemia, and metabolic alkalosis. The presence of an adrenal mass supports this diagnosis.  The principal mineralocorticoid, produced by zona glomerulosa cells of the adrenals, is aldosterone. Synthesis of aldosterone is primarily controlled by the rennin-angiotensin system and is thus involved in control of blood pressure. Reduced or inhibited function in the renin-angiotensin system will lead to excess aldosterone release from the adrenals. Aldosterone causes sodium reabsorption by the kidneys which in turn regulates water balance and leads to increases in blood pressure by increasing fluid volume manifest with the hypertension and hypernatremia evident in this patient.

Question 9

Steroid hormones interact with specific receptors within target cells. The steroid-receptor complexes then regulate the rate of which of the following intracellular processes?

Accepted Answer

Steroid hormones bind to intracellular receptors, forming complexes that act as transcription factors to regulate the transcription of specific genes.  Steroid hormones are lipophilic and hence freely penetrate the plasma membrane of all cells. Within target cells, steroid hormones interact with specific receptors. These receptor proteins are composed of 2 domains: a hormone-binding domain and a DNAbinding domain. Following hormone-receptor interaction the complex is activated and enters the nucleus. The DNA-binding domain of the receptor interacts with specific nucleotide sequences termed hormone response elements (HREs). The binding of steroidreceptor complexes to HREs results in an altered rate of transcription of the associated gene(s). The effects of steroid-receptor complexes on specific target genes can be either stimulatory or inhibitory with respect to the rate of transcription

Question 10

A baby girl is born with ambiguous genitalia and diagnosed with severe classical congenital deficiency of adrenal 21-hydroxylase enzyme. Without any treatment, which of the following would you expect in the girl's future?

Accepted Answer

Without treatment, a deficiency in 21-hydroxylase leads to salt-wasting crises due to the inability to produce sufficient aldosterone, resulting in loss of sodium.  Because CYP21A2 is also needed for the synthesis of aldosterone, which is a major hormone involved in Na+ retention by the kidney, there is excessive salt loss leading to hyponatremic dehydration which can be fatal if not treated. Although there is some aldosterone made, the level of salt loss exceeds the ability of the adrenal cortex to make sufficient aldosterone to compensate. The net result is an acute adrenal crisis.

Question 11

High-dose glucocorticoid therapy for treatment
Of rheumatoid arthritis remains highly controversial. It is widely agreed that it is highly effective in controlling acute rheumatoid inflammation, but it may also result in significant adverse effects. Complications of high-dose glucocorticoid therapy include which of the following?

Accepted Answer

High-dose glucocorticoid therapy can suppress the hypothalamic-pituitary-adrenal axis, leading to adrenal insufficiency when the therapy is stopped abruptly.  High-dose exogenous glucocorticoids suppress the adrenal neuroendocrine axis. Patients treated for longer than 2 weeks need to be tapered off glucocorticoids slowly to avoid adrenal insufficiency. Other complications of high-dose glucocorticoids include growth suppression in children and volume overload. Hyperkalemia and hyponatremia are observed in adrenal insufficiency due to loss of mineralocorticoid effects and are not relevant to glucocorticoid therapy.

Question 12

A 4-year-old child with signs of precocious (earlyonset) puberty is brought to a clinic for evaluation and found to have a congenital deficiency of 21-hydroxylase. Feedback inhibition of the pituitary gland is lost and excess ACTH is secreted. As
A result, which of the following happens?

Accepted Answer

A deficiency in 21-hydroxylase leads to an accumulation of precursors to cortisol synthesis, such as 17-hydroxyprogesterone, because the pathway to produce cortisol is blocked.  In the adrenogenital syndrome the failure to make cortisol due to lack of the adrenal enzyme 21-hydroxylase results in an inability to provide negative feedback suppression of ACTH production. As a result, the adrenal glands are under constant stimulation to maximize steroidogenesis. Substrates that cannot reach cortisol flow down other pathways and by mass action drive the massive overproduction of androgens, which can also be peripherally aromatized to estrogens.

Question 13

A 35-year-old weightlifter who has been injecting testosterone for muscle mass augmentation is evaluated for sterility and found to have an extremely low sperm count. Which of the following is an effect of testosterone and contributes to the mentioned sterility?

Accepted Answer

Exogenous testosterone suppresses the hypothalamic-pituitary-gonadal axis, leading to feedback inhibition of GnRH, which reduces LH and FSH secretion, ultimately decreasing spermatogenesis and causing low sperm count.  Testosterone directly inhibits the secretion of GnRH from the hypothalamus, which affects secretion of LH and FSH and consequently secretion of testosterone. To initiate spermatogenesis, both FSH and testosterone are necessary. To maintain spermatogenesis after puberty, extremely high concentrations of testosterone seem to be required. Systemically administered testosterone does not raise the androgen level in the testes to as great a degree and it additionally inhibits LH secretion. Consequently, the net effect is generally a decrease in sperm count

Question 14

A 40-year-old woman complains of chronic fatigue, aching muscles, and general weakness. Physical examination reveals a modest weight gain, dry skin, and slow reflexes. Laboratory findings include TSH: >10 mU/L (normal range 0.5-5 mU/L), free T4: low to normal. Which of the following is the most likely explanation?

Accepted Answer

The symptoms and lab findings are consistent with hypothyroidism, specifically primary hypothyroidism due to autoimmune thyroid disease (such as Hashimoto's thyroiditis), characterized by elevated TSH and low to normal free T4.  The described symptoms are typical for hypothyroidism. A primary thyroid gland deficiency leads to low T4 levels and high TSH levels. The most common cause of thyroid gland failure is called autoimmune thyroiditis or Hashimoto thyroiditis. It develops slowly due to persistent inflammation of the thyroid caused by the patient's own immune system. Middle-aged women are most commonly affected. The measurement of elevated TSH levels in blood is of high diagnostic value since it helps determine even minor degrees of hypothyroidism. Correct diagnosis is critical because treatment usually continues for life, and stopping of the treatment and reevaluating the original diagnosis is often difficult.

Question 15

A newly wed 23-year-old woman and her 28-yearold husband are evaluated for infertility. They have
Been unable to conceive a child despite regular
Intercourse for the past 12 months. The first step
Of this couple's infertility workup is to determine
Whether ovulation occurs regularly. Which of the
Following hormones is directly responsible for
Ovulation?

Accepted Answer

Luteinizing hormone (LH) is directly responsible for triggering ovulation by causing the mature ovarian follicle to release an egg.  Although the early maturation of an ovarian follicle depends on the presence of FSH, ovulation is induced by a surge of LH. Although estrogens usually have a negative feedback effect on LH and FSH secretion, the LH surge seems to be a response to elevated estrogen levels. In concert with FSH, LH induces rapid follicular swelling. LH also acts directly on the granulosa cells, causing them to decrease estrogen production, as well as initiating production of small amounts of progesterone. These changes lead to ovulation.

Question 16

A baby girl is born with ambiguous genitalia and diagnosed with severe classical congenital deficiency of adrenal 21-hydroxylase enzyme. Without any treatment, which of the following would you expect in the girl's future?

Accepted Answer

Without treatment, a deficiency in 21-hydroxylase leads to impaired cortisol and aldosterone synthesis, causing salt-wasting crises due to loss of sodium.  CYP21A2 (21-hydroxylase) deficiency is the most common enzyme defect in the adrenal gland. In one form of the disorder, called the "salt-wasting" form, aldosterone synthesis is impaired. This is due to the fact that progesterone cannot be converted to 11-deoxycorticosterone, an intermediate on the adrenal mineralocorticoid pathway toward aldosterone. The lack of aldosterone leads to a lack of sodium reabsorption by the distal renal tubules and hence to low serum sodium concentrations. If untreated, hyponatremic dehydration, hyperkalemia, and metabolic acidosis develop. By the second or third week of life, continuous dehydration, worsened by vomiting, leads to circulatory collapse, termed saltwasting crisis. The lack of 21-hydroxylase also leads to a decrease of cortisol synthesis. This is due to the fact that 17α-hydroxyprogesterone cannot be converted to 11-deoxycortisol, the precursor of cortisol. By feedback regulation, low serum cortisol concentration results in increased production of ACTH. Increased ACTH leads to adrenal gland hyperstimulation and increased production of adrenal androgens, which results in precocious puberty. In the moderate form of classical 21-hydroxlyase deficiency, virilization before puberty is the most prevalent symptom.

Question 17

Cushing syndrome is characterized by rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity). Another common sign is the growth of fat pads along the collar bone and on the back of the neck (buffalo hump) and a round face often referred to as a "moon face" and excessive "sweating." This disorder results from overproduction of which of the following hormones?

Accepted Answer

Cushing syndrome is caused by overproduction of cortisol, often due to excessive production of ACTH (Adrenocorticotropic hormone) which stimulates cortisol release from the adrenal glands.  Cushing syndrome most often results from pituitary corticotrope adenomas resulting in excess ACTH production and secretion. The characteristic features of Cushing syndrome are psychiatric disturbances (depression, mania, and psychoses), central obesity, hypertension, diabetes, moon-shaped face, thin fragile skin, easy bruising, and purple striae (stretch marks). In addition, Cushing syndrome patients manifest with gonadal dysfunction that is characteristic of hyperandrogenism with excess body and facial hair (hirsutism) and acne.

Question 18

You are treating a 37-year-old female patient whose signs and symptoms lead you to suspect she is suffering from an endocrine disorder. You order a series of tests to aid in your diagnosis. A basic metabolic panel showed elevated sodium of 111 mmol/L (normal range 135-145), potassium 4.5 mmol/L, chloride 78 mmol/L, bicarbonate 23 mmol/L, glucose 85 mg/dL, and creatinine 0.7 mg/dL. Further testing showed serum osmolality at 234 mOsm/kg (normal range 275-295) and urine sodium less than 20 mmol/L consistent with severe hypovolemic hyponatremia. A random cortisol level was less than 0.2 μg/dL. The plasma ACTH level was elevated at 882 pg/dL (normal range 5-27). These test results most likely indicate the patient is suffering from which of the following disorders?

Accepted Answer

The patient has severe hyponatremia, low cortisol, and elevated ACTH, which are indicative of primary adrenal insufficiency, also known as Addison's disease.  Addison disease results from a primary failure of the adrenal cortex to synthesize and secrete glucocorticoid (cortisol) and mineralocorticoid (aldosterone) hormones resulting in metabolic disturbances. Electrolytes (sodium, potassium, chloride, and carbon dioxide) are measured to help detect and evaluate the severity of an existing electrolyte imbalance characteristic of Addison disease. With Addison disease, the sodium, chloride, and carbon dioxide levels are often low, while the potassium level may be very high. If the adrenal gland is either not functioning normally or not being stimulated by ACTH, then cortisol levels will be consistently low.

Question 19

You are treating a 29-year-old woman who came to you complaining of a 3-month history of increased sweating and palpitations with weight loss of 15 lb. Physical examination shows she is nervous and agitated with an obvious, diffuse, nontender, smooth enlargement of her thyroid, over which a bruit could be heard. She had a fine tremor of her fingers and a resting pulse rate of 150/min. Laboratory studies indicate the elevated serum T₃ of 4.8 nmol/L (normal: 0.8-2.4) and a T₄ of 48 nmol/L (normal: 9-23). Measurement of her thyroid-stimulating hormone showed that it was low normal, 0.4 mU/L (normal 0.4-5 mU/L). The signs and symptoms exhibited by your patient most likely indicate she is suffering from which of the following?

Accepted Answer

The symptoms and lab findings are consistent with Graves disease, an autoimmune disorder that causes hyperthyroidism. The diffuse thyroid enlargement with a bruit, elevated T3 and T4, and low TSH are characteristic of Graves disease.

Question 20

Cells of the zona fasciculata of the adrenal cortex do not synthesize the potent mineralocorticoids because they lack expression of which of the following enzymes?

Accepted Answer

The zona fasciculata lacks CYP11B2, aldosterone synthase, which is necessary for the synthesis of mineralocorticoids like aldosterone. This enzyme is expressed in the zona glomerulosa.  Cells of the zona fasciculata and zona reticularis do not express aldosterone synthase (CYP11B2; 18α-hydroxylase; P450c18) that converts corticosterone to aldosterone, and thus these tissues produce only the weak mineralocorticoid corticosterone.

Quiz 50: Steroid and Thyroid Hormones

Which of the following processes is induced in males in response to the synthesis and release of follicle-stimulating hormone (FSH) ?

Which of the following is true with respect to the actions of the mineralocorticoids?

Steroid hormones interact with specific receptors within target cells. The steroid-receptor complexes then regulate the rate of which of the following intracellular processes?

A baby girl is born with ambiguous genitalia and diagnosed with severe classical congenital deficiency of adrenal 21-hydroxylase enzyme. Without any treatment, which of the following would you expect in the girl's future?

A 4-year-old child with signs of precocious (earlyonset) puberty is brought to a clinic for evaluation and found to have a congenital deficiency of 21-hydroxylase. Feedback inhibition of the pituitary gland is lost and excess ACTH is secreted. As A result, which of the following happens?

A 35-year-old weightlifter who has been injecting testosterone for muscle mass augmentation is evaluated for sterility and found to have an extremely low sperm count. Which of the following is an effect of testosterone and contributes to the mentioned sterility?

A baby girl is born with ambiguous genitalia and diagnosed with severe classical congenital deficiency of adrenal 21-hydroxylase enzyme. Without any treatment, which of the following would you expect in the girl's future?

Cells of the zona fasciculata of the adrenal cortex do not synthesize the potent mineralocorticoids because they lack expression of which of the following enzymes?