Endocrinology 4

oelomar's version from 2016-02-27 14:39


Question Answer
What is Addison’s disease?Also called hypoadrenalism, there is destruction of the entire adrenal cortex (this can be autoimmune or as a result of certain infection (or rarer causes)). As a result, cortisol and aldosterone production is reduced.
What are the causes of Addison’s disease?Autoimmune disease is the most common cause in the UK. Worldwide, the most common cause is TB.
What are the clinical features of Addison’s disease?It is characterised by a number of relatively non-specific symptoms such as abdominal pain and weakness, but under certain circumstances, these may progress to Addisonian crisis. Reduced cortisol levels leads to increased CRH and ACTH production (from the hypothalamus and pituitary gland respectively), the latter being directly responsible for hyperpigmentation (grey-brown) of the skin. Postural systolic hypertension is also present in 90% of cases.
What is Addisonian crisis?A constellation of symptoms including severe hypotension and coma that indicate severe adrenal insufficiency caused by insufficient levels of the hormone cortisol. It is a medical emergency and potentially life-threatening situation requiring immediate emergency treatment.
What is Waterhouse-Friderichsen syndrome?Also known as haemorrhagic adrenalitis, WFS is defined as adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection. Typically the pathogen is the meningococcus Neisseria meningitides. The bacterial infection leads to massive haemorrhage into one or (usually) both adrenal glands. It is characterised by overwhelming bacterial infection meningococcemia leading to massive blood invasion, organ failure, hypotension, coma, rapidly developing adrenocortical insufficiency, and death.
What is the synacthen test?Also known as the ACTH stimulation test, this is a test of adrenal insufficiency. During the test, a small amount of synthetic ACTH is injected, and the amount of cortisol, and sometimes aldosterone, the adrenal glands produce in response is measured. In healthy individuals, the cortisol level should double from a baseline of 20-30 µg/dl within 60 minutes. An absent/impaired cortisol response confirms the presence of hypoadrenalism but does not differentiate Addison’s disease from ACTH deficiency or iatrogenic suppression by steroid medication.
How is Addison’s disease treated?Long-term treatment is with replacement glucocorticoid and mineralocorticoid. An example is Hydrocortisone + fludrocortisone.
What is the difference between primary and secondary adrenal insufficiency?Primary adrenal insufficiency is due to impairment of the adrenal glands. 80% of primary adrenal insufficiency is due to Addison’s disease. Secondary adrenal insufficiency is caused by impairment of the pituitary gland or hypothalamus. Secondary adrenal insufficiency has no skin hyperpigmentation and no hyperkalaemia.
Why do patients with adrenal insufficiency need T4 replacement?Because these patients have panhypopituitarism, and therefore need T4 replacement as well as cortisol. Note that people with Addison's disease often have an underactive thyroid gland, and hypothyroidism may mask the Addison's disease.
How is acute hypoadrenalism managed?Treated with IV hydrocortisone, 0.9% saline, and glucose.


Question Answer
What is the most common cause of secondary hypoadrenalism?Abrupt cessation of chronic glucocorticoid treatment.
Describe the hypothalamic-pituitary-adrenal axis.Hypothalamus secrete corticotropin releasing hormone (CRH); CRH causes anterior pituitary to secrete adrenocorticotropic hormone (ACTH); ACTH causes adrenal cortex to secrete cortisol.
What is Cushing’s syndrome?Cushing’s syndrome is the term used to describe the clinical state of increased free circulating glucocorticoid.
What are the clinical features of Cushing’s syndrome?Hypertension, central obesity, muscle wasting, thin skin with purple striae, psychological disturbances, hirsutism, moon facies, “buffalo hump”, depression, oligomenorrhoea, growth retardation, proximal weakness.
What are the causes of Cushing’s syndrome?Hypersecretion of ACTH from a pituitary adenoma (Cushing’s disease) (65% of cases), an “ectopic” ACTH producing tumour elsewhere in the body (10%), a primary excess of endogenous cortisol secretion (25% of spontaneous cases) by an adrenal tumour or nodular hyperplasia, with subsequent suppression of ACTH, and iatrogenic factors (taking of glucocorticoids to treat other diseases).
What is pseudo-Cushing’s syndrome?Pseudo-Cushing's syndrome is a medical condition in which patients display the signs, symptoms, and abnormal hormone levels seen in Cushing’s syndrome. However, pseudo-Cushing's syndrome is not caused by a problem with the hypothalamic-pituitary-adrenal axis as Cushing's is; it is mainly an idiopathic condition, however a cushingoid appearance is sometimes linked to excessive alcohol consumption.
What is the dexamethasone suppression test?The dexamethasone suppression test (DST) is used to assess adrenal gland function by measuring how cortisol levels change in response to an injection of dexamethasone. It is typically used to diagnose Cushing’s syndrome.
How does the dexamethasone suppression test work?Dexamethasone is an exogenous steroid that provides negative feedback to the pituitary gland to suppress the secretion of ACTH. Specifically, dexamethasone binds to glucocorticoid receptors in the anterior pituitary gland. Patients with Cushing’s syndrome fail to suppress cortisol levels (with the low-dose variation of the test).
What are the different variations of the dexamethasone suppression test?Low-dose and high-dose. A low dose of dexamethasone suppresses cortisol in individuals with no pathology in endogenous cortisol production. A high dose of dexamethasone exerts negative feedback on pituitary ACTH-producing cells, but not on ectopic ACTH-producing cells or adrenal adenoma.
How is Cushing’s syndrome treated?It depends on the cause. Iatrogenic = stop medications. Cushing’s disease = Trans-sphenoidal removal of the tumour or bilateral adrenalectomy if source unlocatable. Adrenal adenoma = adrenalectomy. Ectopic ACTH = surgery to remove tumour. Metyrapone can be given (blocks cortisol synthesis). Ketoconazole (an anti-fungal) can also be of help.


Question Answer
What is Nelson’s syndrome?This is the rapid enlargement of a pre-existing ACTH-secreting pituitary adenoma which occurs in about 20% of cases after bilateral adrenalectomy for Cushing’s disease. The common signs and symptoms include muscle weakness and skin hyperpigmentation.
Is Nelson’s syndrome common nowadays? Why?Nelson’s syndrome is rare nowadays. This is because bilateral adrenalectomy is now only used in extreme circumstances, and its incidence may be reduced by pituitary radiotherapy soon after adrenalectomy.
What is congenital adrenal hyperplasia (CAH)?CAH are any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis). All lead to cortisol deficiency. Cortisol deficiency stimulates ACTH synthesis and → overproduction of adrenal androgens through adrenal hyperplasia.
What is the most common type of congenital adrenal hyperplasia?21-hydroxylase deficiency (21-OH), which is responsible for around 95% of CAH.
What are the clinical features of congenital adrenal hyperplasia?Ambiguous genitalia in female infants (genitals don’t appear to be clearly either male or female) or virilisation (if manifested later in life); macrogenitosomia in male infants (excessive bodily and genital development)or precocious puberty (if manifested later in life); hypertension (with 11- and 17-hydroxylase deficiencies); hypotension (with 21-hydroxylase deficiency).
How is congenital adrenal hyperplasia treated?Cortisol administration to decrease ACTH and adrenal androgens. Fludrocortisone is given for severe 21-hydroxylase deficiency.
What is diabetes insipidus?A condition characterised by excessive thirst and secretion of large volumes of dilute urine, with reduction of fluid intake having no effect on the concentration of the urine. This happens as a result of reduced ADH secretion from the posterior pituitary (cranial DI), or impaired response of the kidney to ADH (nephrogenic DI). DI also results in hypernatraemia.
What is the most common cause of diabetes insipidus?Hypothalamic–pituitary surgery, following which transient DI is common, frequently remitting after a few days or weeks.
How is diabetes insipidus treated?Cranial DI is treated with desmopressin (synthetic ADH). Nephrogenic DI is treated by treating the underlying cause, and if unsuccessful, a thiazide diuretic is given.
Name some causes of nephrogenic diabetes insipidus.In this condition, renal tubules are resistant to vasopressin. It may be inherited or more commonly acquired as a result of renal disease, sickle cell disease, drug ingestion (e.g. lithium), hypercalcaemia or hypokalaemia.


Question Answer
How is diabetes insipidus diagnosed?With the water deprivation test, which is a test which can be used to determine whether the patient has diabetes insipidus as opposed to other causes of polydipsia. The patient is deprived of fluid for a period of time ranging from 4-18 hours. The urine osmolality is then measured. If it doesn’t go up, then the patient has diabetes insipidus. Response to desmopressin distinguishes between central and nephrogenic DI.
What are the signs/symptoms of SIADH?SIADH leads to retention of water (hypervolaemia) and hyponatraemia. The presentation is usually vague, with confusion, nausea, irritability and, later, fits and coma. There is no oedema.
How is SIADH diagnosed?Laboratory findings are used to diagnose SIADH. Findings include euvolaemic hyponatraemia, low plasma osmolality with higher urine osmolality, and continued urine sodium excretion of >40mEq/L despite normal dietary salt intake. Other findings include absence of hypokalaemia (or hypotension).
How is SIADH treated?The underlying causes should be treated when possible. Otherwise, Fluid intake should be restricted to 500–1000 mL daily. If tolerated this will correct the biochemical abnormalities in almost every case. If water restriction is poorly tolerated, demeclocycline is given; this inhibits the action of vasopressin on the kidney. When the syndrome is very severe, hypertonic saline may be indicated but this is potentially dangerous and should only be used with extreme caution.
What is demeclocycline and what are its side effects?Demeclocycline is a tetracycline antibiotic which also works as an ADH antagonist. Side effects include nephrogenic diabetes insipidus, photosensitive rashes, and abnormalities of bone and teeth.
What are the most common causes of hypercalcaemia?Hyperparathyroidism and malignancies are by far the most common causes (> 90% of cases). Severe hypercalcaemia is also associated with vitamin D deficiency.
What are the signs/symptoms of hypercalcaemia?May be asymptomatic. Otherwise, symptoms are classically summarised by the mnemonic “stones (kidney), bones (bone pain, myalgias, arthralgias, fractures), abdominal groans (abdominal pain, nausea, vomiting, peptic ulcer disease, pancreatitis), thrones (polyuria and constipation) and psychiatric overtones (lethargy, fatigue, depression, anxiety, memory loss, etc.).
What are the signs/symptoms of hyperparathyroidism?The same as those of hypercalcaemia. They are classically summarised by the mnemonic “stones (kidney), bones (bone pain, myalgias, arthralgias, fractures), abdominal groans (abdominal pain, nausea, vomiting, peptic ulcer disease, pancreatitis), thrones (polyuria and constipation) and psychiatric overtones (lethargy, fatigue, depression, anxiety, memory loss, etc.).
How is primary hyperparathyroidism treated, and what is the major side effect of this treatment?Treatment is by total parathyroidectomy. The major danger after operation is transient hypocalcaemia.
How is acute severe hypercalcaemia treated?IV 0.9% saline. Intravenous bisphosphonates (such as pamidronate) are also used as treatment.


Question Answer
What are bisphosphonates and what are they used to treat? Also, name a bisphosphonate.Bisphosphonates are a class of drug that prevent the loss of bone mass. They are used to treat osteoporosis and similar diseases. An example of one is pamidronate.
What are the causes of hypocalcaemia?Chronic kidney disease (most common cause), post-thyroid surgery (but this is usually transient hypocalcaemia), idiopathic hypocalcaemia (rare autoimmune disorder).
With regards to hypoparathyroidism, what is DiGeorge syndrome?DiGeorge syndrome is a familial condition in which there is hypoparathyroidism also associated with intellectual impairment, cataracts, and calcified basal ganglia.
What is the difference between primary and secondary hyperparathyroidism?Primary hyperparathyroidism is usually caused by a tumour within the parathyroid gland. Secondary hyperparathyroidism refers to the excessive secretion of parathyroid hormone (PTH) by the parathyroid glands in response to hypocalcaemia (low blood calcium levels) and associated hypertrophy of the glands.
What is pseudohypoparathyroidism and what is its clinical manifestations?Pseudohypoparathyroidism is a rare condition associated primarily with resistance to PTH, which leads to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms. It is also associated with short stature, short 4th & 5th fingers, subcutaneous calcification and sometimes intellectual impairment.
What is pseudopseudohypoparathyroidism?An inherited disorder in which the individual has the phenotypic appearance of pseudohypoparathyroidism, but is biochemically normal, i.e. appearance will show skeletal defects, but levels of PTH, calcitriol, calcium, and phosphates are normal.
What are the clinical features of hypoparathyroidism?Hypoparathyroidism presents as neuromuscular irritability and neuropsychiatric manifestations. Paraesthesiae, circumoral numbness, cramps, anxiety and tetany are followed by convulsions, laryngeal stridor, dystonia and psychosis. Chronically it can lead to cataracts.
What may severe hypocalcaemia show on ECG?Prolonged QT interval.
What is Chvostek’s sign and what does it indicate?The Chvostek sign is a clinical sign of existing nerve hyperexcitability (tetany) seen in hypocalcaemia. It refers to an abnormal reaction to the stimulation of the facial nerve. When the facial nerve is tapped at the angle of the jaw (i.e. masseter muscle), the facial muscles on the same side of the face will contract momentarily (typically a twitch of the nose or lips) because of hypocalcaemia.