Endocrine Flashcards
(104 cards)
What enzyme-deficiency is this?
11β-Hydroxylase deficiency is suggested by the constellation of hypertension, masculinization, and hypokalemia.
How is 11β-Hydroxylase deficiency differentiated from a more common, but similar, enzyme deficiency?
21β-Hydroxylase deficiency presents with hypotension and hyperkalemia. Both deficiencies present with masculinization of the external genitalia. A review of adrenal steroid synthesis is shown in Figure 6-1.
How does 11β-Hydroxylase deficiency result in hypertension?
11β-Hydroxylase converts 11-deoxycorticosterone into corticosterone, and 11-deoxycortisol into cortisol. 11β-Hydroxylase deficiency causes a lack of cortisol and aldosterone. However, the precursor 11-deoxycortisone is a weak mineralocorticoid and causes hypertension.
What is the appropriate treatment for 11β-Hydroxylase deficiency?
Dexamethasone or hydrocortisone can be used to replace the missing corticosteroid. The lowest effective dose should be used to avoid the Cushingoid adverse effects of glucocorticoids, including bone demineralization and growth retardation.
What is the mode of inheritance of 11β-Hydroxylase deficiency?
Inheritance is autosomal recessive, with mutations in the CYP11B1 gene. All of the congenital adrenal hyperplasias are inherited in an autosomal recessive manner.
What is the most likely diagnosis? What enzyme deficiency is responsible for this condition?
The patient’s ambiguous external genitalia (masculinization) and hypotension suggest congenital adrenal hyperplasia. These signs are caused by lack of cortisol and aldosterone.
The defective enzyme is 21β-hydroxylase, an enzyme in the pathway that converts cholesterol into aldosterone and cortisol (Figure 6-1). This leads to excess substrates, which are shunted toward synthesis of sex hormones. Decreased cortisol leads to loss of feedback inhibition, increased adrenocorticotropic hormone, and further stimulation of the conversion of cholesterol into sex hormone precursors.
What are the likely findings on laboratory testing in 21β-hydroxylase deficiency?
Hyponatremia and hyperkalemia are likely because mineralocorticoids (which are low in these patients) are responsible for the retention of sodium and the excretion of potassium. Salt wasting causes hypotension, which leads to activation of the renin-angiotensin system, resulting in elevated serum renin levels.
Is this an example of hermaphroditism or pseudohermaphroditism?
Pseudohermaphroditism is a condition in which an infant is born with the gonads of one sex and the external genitalia of the opposite sex (eg, normal female gonads but ambiguous, male-like external genitalia). True hermaphroditism (rare) occurs when the infant has both male and female gonadal tissue.
What is the appropriate treatment for this condition - 21β-hydroxylase deficiency?
Treatment consists of replacement of the deficient hormones.
What is the most likely diagnosis?
Addison disease, or primary adrenal insufficiency, is suggested by the clinical history of weakness and orthostatic hypotension and by the signs of hyperpigmentation, hyponatremia, hyperkalemia, and a low serum cortisol level.
What are 7 common etiologies of Addison’s disease?
Most cases of Addison disease are idiopathic or autoimmune related. Other causes include the following:
1. Disseminated intravascular coagulation.
2. Waterhouse-Friderichsen syndrome (hemorrhagic necrosis of the adrenal gland, classically due to meningococcemia).
3. Granulomatous diseases such as tuberculosis.
4. HIV infection.
5. Neoplasm.
6. Trauma.
7. Iatrogenic vascular disorders.
What is the cause of this patient’s metabolic abnormalities?
Adrenal insufficiency causes a deficiency of cortisol. Hyponatremia, hyperkalemia, and a low bicarbonate level can result from low aldosterone levels associated with primary adrenal insufficiency.
How would this patient, with Addisons disease, cortisol level change if she were administered adrenocorticotropic hormone (ACTH)?
The cortisol level should not change appreciably since it is low because of a primary adrenal insufficiency (ie, the problem is within the adrenal gland itself). This is suggested by the hyperpigmentation, which is due to the attempt of the pituitary gland to overcome the cortisol deficiency by increasing ACTH production. ACTH, in turn, stimulates the release of melanocyte-stimulating hormone, causing hyperpigmentation.
What are the secondary and tertiary forms of Addison’s disease?
Secondary adrenal insufficiency is caused by decreased ACTH secretion by the pituitary gland. Administration of ACTH results in a cortisol response. This syndrome does not cause hyperpigmentation. Tertiary adrenal insufficiency is caused by a decrease in corticotropin-releasing hormone production by the hypothalamus.
What is the most likely diagnosis?
Primary hyperaldosteronism, also known as Conn syndrome, is suggested by the patient’s history and her hypertension, hypernatremia, and hypokalemia. Approximately 30%–60% of cases are due to solitary adrenal adenomas in the zona glomerulosa, the aldosterone-secreting layer of the adrenal cortex. Bilateral hyperplasia of the zona glomerulosa can also cause Conn syndrome.
How is aldosterone regulated?
Renin, produced by the juxtaglomerular cells of the kidney, cleaves angiotensinogen (produced by the liver) to form angiotensin I. Angiotensin I, in turn, is cleaved by angiotensin-converting enzyme to form angiotensin II. In response to volume contraction, angiotensin II becomes a potent stimulator of aldosterone synthase, a key enzyme in aldosterone synthesis.
Other key stimuli of aldosterone secretion include decreased plasma sodium and increased plasma potassium.
Another patient presents with similar symptoms, but his laboratory tests show increased serum renin activity. What is his most likely diagnosis?
Another patient presents with similar symptoms, but his laboratory tests show increased serum renin activity. What is his most likely diagnosis?
Given the patient’s serum potassium level of 2.8mEq/L, what are the most likely findings on electrocardiogram (ECG)?
Typical ECG findings include prominent U waves, flattened T waves, and ST-segment depression (Figure 6-2).
What is the appropriate treatment for Primary hyperaldosteronism (Conn syndrome), and what are the adverse effects?
If a solitary, aldosterone-secreting adrenal adenoma is found, surgical resection (adrenalectomy) is indicated. Bilateral adrenal hyperplasia is treated medically with an aldosterone antagonist such as spironolactone. Major adverse effects of spironolactone are due to its antiandrogen effects, including gynecomastia, loss of libido, menstrual irregularities, and impotence.
What is the most likely diagnosis? 4 common causes?
Cushing syndrome results from excess glucocorticoids, either from increased cortisol production or exogenous glucocorticoid therapy. Common causes include the following:
1. Iatrogenic (eg, steroid ingestion, most common).
2. Pituitary adenoma (Cushing disease).
3. Adrenal tumor/hyperplasia.
4. Adrenocorticotropic hormone (ACTH)-producing tumor (most commonly secondary to small cell lung cancer).
What laboratory tests can help confirm the diagnosis of Cushing syndrome?
Screening tools for Cushing syndrome or glucocorticoid excess include the following:
1. 24-hour urine free cortisol test. Elevated cortisol level indicates hypercortisolism.
2. Dexamethasone suppression test. A normal result is a decrease in cortisol after administration of low- dose dexamethasone. In glucocorticoid excess due to Cushing disease, low-dose dexamethasone will
not suppress cortisol levels.
After identifying elevated cortisol levels, what diagnostic tests help define the source of the hormonal abnormality?
What are the appropriate treatments for Cushing syndrome?
The most appropriate treatment for adrenal tumors is surgery. Treatments for nonresectable tumors or hyperplasia are as follows:
1. Ketoconazole: Inhibits glucocorticoid production.
2. Metyrapone: Inhibits cortisol formation in adrenal pathway.
3. Aminoglutethimide: Inhibits the synthesis of steroids.
What is the regular cycle of cortisol levels in the body?
Cortisol levels peak in the early morning (approximately 8 AM) and reach their lowest levels at midnight. Basal body temperature fluctuates with the cortisol cycle (Figure 6-3).
